Therapeutic drug monitoring of nevirapine in resource-limited settings.

NARCIS (Netherlands)

L'homme, R.F.A.; Muro, E.P.; Droste, J.A.H.; Wolters, L.R.; Ewijk-Beneken Kolmer, E.W.J. van; Schimana, W.; Burger, D.M.

2008-01-01

BACKGROUND: We developed a simple and inexpensive thin-layer chromatography (TLC) assay for semiquantitative detection of saliva concentrations of nevirapine in resource-limited settings. The method was validated in an African target population. METHODS: Paired plasma and saliva nevirapine

Maternal deaths following nevirapine-based antiretroviral therapy

Directory of Open Access Journals (Sweden)

E Bera

2012-10-01

Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.

The Association Between Skin Rashes and Work Environment, Personal Protective Equipment, and Hygiene Practices Among Female Farmworkers.

Science.gov (United States)

Campbell, Kristina; Baker, Brenda; Tovar, Antonio; Economos, Eugenia; Williams, Bryan; McCauley, Linda

2017-07-01

The objective of this study was to assess work-related hygiene practices and the frequency and location of skin rashes due to cutaneous contact with crop-associated materials (e.g., pesticides) for female nursery and fernery workers in Central Florida. A cross-sectional, community-based participatory research study of 237 female nursery and fernery workers between the ages of 19 and 43 years with significant cutaneous contact with foliage crops was conducted using a self-report questionnaire and a skin rash chart assessment tool. Of the 237 farmworkers surveyed, 37.1% ( n = 88) reported a rash on at least one area of their bodies. Women who were pregnant during the study were 4.7 times more likely to report more than 30% total body surface area (TBSA) covered by rash compared with non-pregnant fernery workers ( p = .045; 95% confidence interval [CI] [1.04, 21.35]). Further research is needed to better understand the development of skin rashes among farmworkers, to generate effective prevention strategies.

Skin rash during treatment with generic itraconazole.

Science.gov (United States)

De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

2014-04-01

Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re-challenge confirmed the association between itraconazole and skin rash. Both Naranjo probability scale and World Health Organization causality assessment scale documented a probable association between generic-itraconazole and skin rash. The switch from generic formulation to brand one induced an improvement of symptoms. Since we are unable to evaluate the role of each excipient in the development of skin rash, we cannot rule out their involvement. However, more data are necessary to better define the similarities or differences between branded and generic formulations.

Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

Energy Technology Data Exchange (ETDEWEB)

Oliveira, G.G.G. de; Ferraz, H.G. [Department of Pharmacy, Faculty of Pharmaceutical Health, University of Sao Paulo, Sao Paulo 05508-900 (Brazil); Severino, P. [Department of Biotechnological Processes, School of Chemical Engineering, University of Campinas, Campinas 13083-970 (Brazil); Department of Pharmaceutical Technology, Faculty of Health Sciences, Fernando Pessoa University, Porto 4200-150 (Portugal); Souto, E.B., E-mail: eliana@ufp.edu.pt [Department of Pharmaceutical Technology, Faculty of Health Sciences, Fernando Pessoa University, Porto 4200-150 (Portugal); Institute for Biotechnology and Bioengineering, Centre for Genomics and Biotechnology, University of Tras-os-Montes e Alto Douro (IBB-CGB/UTAD), 5001-801 Vila Real (Portugal)

2013-03-01

Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug. - Graphical abstract: Bulk nevirapine powder analysed by scanning electron microscopy and the drug solubility profile in various buffer solutions. The pH values of the media in which the tests were conducted are also presented. Highlights: Black-Right-Pointing-Pointer Nevirapine shows more than one crystalline form, that influence its in vivo and in vitro behaviour. Black-Right-Pointing-Pointer DSC and TGA were used for solid-state characterization of crystalline forms of nevirapine. Black-Right-Pointing-Pointer Nevirapine is compatible with lactose, microcrystalline cellulose, PVP/PVA copolymers and HPMC. Black

Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART

International Nuclear Information System (INIS)

Oliveira, G.G.G. de; Ferraz, H.G.; Severino, P.; Souto, E.B.

2013-01-01

Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug. - Graphical abstract: Bulk nevirapine powder analysed by scanning electron microscopy and the drug solubility profile in various buffer solutions. The pH values of the media in which the tests were conducted are also presented. Highlights: ► Nevirapine shows more than one crystalline form, that influence its in vivo and in vitro behaviour. ► DSC and TGA were used for solid-state characterization of crystalline forms of nevirapine. ► Nevirapine is compatible with lactose, microcrystalline cellulose, PVP/PVA copolymers and HPMC. ► The acid form of nevirapine is the most appropriate for assessing release profile from

Fever and rash.

Science.gov (United States)

Schlossberg, D

1996-03-01

The combination of fever and rash comprises an extensive differential diagnosis. Many of the causes of this presentation are life-threatening. In this article, rashes are categorized as petechial, maculopapular, vesicular, erythematous, and urticarial. Each type of rash is then divided into infectious etiologies, both treatable and nontreatable, and noninfectious etiologies. It is usually possible to arrive at a workable differential diagnosis when clinical, historical, and epidemiologic factors are considered.

Efficacy and durability of nevirapine in antiretroviral drug naive patients

NARCIS (Netherlands)

Lange, Joep M. A.

2003-01-01

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) naive patients. Four key studies have

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study.

Science.gov (United States)

Monera-Penduka, Tsitsi G; Maponga, Charles C; Wolfe, Alan R; Wiesner, Lubbe; Morse, Gene D; Nhachi, Charles F B

2017-01-01

Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration-time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (C max ) and concentration at 12 h (C 12h ) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs). Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00-1.14) for the AUC; 1.06 (0.98-1.16) for C max and 1.03 (0.92-1.16) for C 12h . Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov).

What is that rash?

Science.gov (United States)

Speirs, Lynne; McVea, Steven; Little, Rebecca; Bourke, Thomas

2018-02-01

A healthy 15-month-old girl presented to the emergency department with a 24-hour history of fever and rash. The initial blanching rash developed into non-blanching areas with associated leg swelling. She had received no recent medications, had no known drug allergies and no unwell contacts.On examination, she was feverish at 38.6°C, capillary refill time was <2 s with warm peripheries, heart rate 169 bpm and blood pressure 94/59 mm Hg. A palpable purpuric rash was evident on all four limbs and face (figure 1) although the trunk was spared. Her legs were tense and oedematous to the knee.edpract;103/1/25/EDPRACT2016311782F1F1EDPRACT2016311782F1Figure 1Rash at presentation.Initial investigations: Haemoglobin level: 131 g/L, white cell count: 16.6×10 9 /L, neutrophils: 11.1×10 9 /L and platelets: 407×10 9 /LCoagulation screen: normalC reactive protein level: 20 mg/LLactate level: 1.7 mmol/LIntravenous ceftriaxone was commenced following blood culture and meningococcal PCR. The following day, while remaining systemically well, she developed a vesicular rash on her trunk and back (figure 2).edpract;103/1/25/EDPRACT2016311782F2F2EDPRACT2016311782F2Figure 2Vesicular rash. What is the diagnosis? Henoch-Schonlein purpura (HSP)Meningococcal septicaemiaAcute haemorrhagic oedema of infancy (AHOI)Vasculitic urticariaGianotti-Crosti syndromeWhat further investigation is required? Check viral serology including Epstein-Barr virus and hepatitis B virusComplement levels and autoimmune screenSkin biopsyLumbar puncture and audiologyNo further investigationHow should this child be managed? Complete 7 days of ceftriaxone treatmentOral aciclovirOral steroidsRegular follow-up with urinalysis and blood pressure monitoringStop antibiotics if cultures were negative at 48 hours and discharge Answers are on page ▪▪. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Poison Ivy Rash

Science.gov (United States)

Poison ivy rash Overview Poison ivy rash is caused by an allergic reaction to an oily resin called urushiol (u-ROO-she-ol). This oil is in the leaves, stems and roots of poison ivy, poison oak and poison sumac. Wash your ...

Generalized petechial rashes in children during a parvovirus B19 outbreak.

Science.gov (United States)

Edmonson, M Bruce; Riedesel, Erica L; Williams, Gary P; Demuri, Gregory P

2010-04-01

Human parvovirus B19 infection is associated not only with erythema infectiosum (fifth disease) but also, rarely, with purpuric or petechial rashes. Most reports of these atypical rashes describe sporadic cases with skin lesions that have distinctively focal distributions. During a community outbreak of fifth disease, we investigated a cluster of illnesses in children with generalized petechial rashes to determine whether parvovirus was the causative agent and, if so, to describe more fully the clinical spectrum of petechial rashes that are associated with this virus. Systematic evaluation was conducted by general pediatricians of children with petechial rashes for evidence of acute parvovirus infection. During the outbreak, acute parvovirus infection was confirmed in 13 (76%) of 17 children who were evaluated for petechial rash. Confirmed case patients typically had mild constitutional symptoms, and most (11 [85%] of 13) had fever. Petechiae were typically dense and widely distributed; sometimes accentuated in the distal extremities, axillae, or groin; and usually absent from the head/neck. Most case patients had leukopenia, and several had thrombocytopenia. Parvovirus immunoglobulin M was detected in 8 (73%) of 11 acute-phase serum specimens, and immunoglobulin G was detectable only in convalescent specimens. Parvovirus DNA was detected in all 7 tested serum specimens, including 2 acute-phase specimens that were immunoglobulin M-negative. All case patients had brief, uncomplicated illnesses, but 6 were briefly hospitalized and 1 underwent a bone marrow examination. Two case patients developed erythema infectiosum during convalescence. During an outbreak of fifth disease, parvovirus proved to be a common cause of petechial rash in children, and this rash was typically more generalized than described in case reports. Associated clinical features, hematologic abnormalities, and serologic test results are consistent with a viremia-associated illness that is distinct

Incidence of rash after amoxicillin treatment in children with infectious mononucleosis.

Science.gov (United States)

Chovel-Sella, Aluma; Ben Tov, Amir; Lahav, Einat; Mor, Orna; Rudich, Hagit; Paret, Gideon; Reif, Shimon

2013-05-01

"Ampicillin rash," a phenomenon unique to patients with Epstein-Barr virus acute infectious mononucleosis (AIM) treated with ampicillin, was first reported in the 1960s. The incidence was estimated as being between 80% and 100%, and the figures have not been reviewed since those first accounts. We sought to establish the current incidence of rash associated with antibiotic treatment among children with AIM. A retrospective study of all hospitalized children diagnosed as having AIM based upon positive Epstein-Barr virus serology in 2 pediatric tertiary medical centers in Israel. Of the 238 children who met the study entry criteria during the study period, 173 were treated with antibiotics. Fifty-seven (32.9%) of the subjects treated with antibiotics had a rash during their illness compared with 15 (23.1%) in untreated patients (P = .156; not significant). Amoxicillin was associated with the highest incidence of antibiotic-induced rash occurrence (29.5%, 95% confidence interval: 18.52-42.57), but significantly lower than the 90% rate reported for ampicillin in past studies. Age, gender, ethnicity, and atopic or allergic history were not associated with the development of rash after antibiotic exposure. Among the laboratory data, only increased white blood cell counts were more prevalent among subjects who did not develop an antibiotic-induced rash. The incidence of rash in pediatric patients with AIM after treatment with the current oral aminopenicillin (amoxicillin) is much lower than originally reported.

Skin rash and arthritis a simplified appraisal of less common associations.

Science.gov (United States)

Cozzi, A; Doria, A; Gisondi, P; Girolomoni, G

2014-06-01

Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information. © 2013 European Academy of Dermatology and Venereology.

ORIGINAL ARTICLES Nevirapine toxicity- implications for ...

African Journals Online (AJOL)

Nevirapine was the first non-nucleoside drug (NNRTI) to be approved by the ... related toxicities in pregnancy were highlighted by a study published in 2004 ..... health, of consumption of scarce financial resources, of concern about doctors ...

Cephalhematoma and petechial rashes associated with acute parvovirus B19 infection: a case report.

Science.gov (United States)

Takeuchi, Masato; Shiozawa, Ryosuke; Hangai, Mayumi; Takita, Junko; Kitanaka, Sachiko

2013-10-07

Parvovirus B19 can cause petechial rashes in the acute phase of illness as well as erythema infectiosum (fifth disease) during convalescence. This petechial rash is often called "gloves and socks" syndrome because of the typical distribution of the eruption. However, involvement of other sites (e.g., intertriginous area) and generalized involvement have been recently recognized. We report here a patient with parvovirus-associated petechiae and cephalhematoma. The patient was a previously healthy 10-year-old boy. There was a family history of fatal bleeding; his sister died of intracranial bleeding with an uncertain cause at the age of 5 months. The patient was admitted to our hospital because of sudden onset of cephalhematoma associated with fever. He reported that he had no recent head trauma but that he massaged his scalp on the day before admission. On admission, his temperature was 38.8°C; otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes were present on his trunk and limbs. The initial laboratory tests were essentially normal, including platelet count and coagulation tests. Expanded laboratory tests were repeated to explore the etiology of his skin hemorrhage, all of which indicated that hematological disorders were unlikely. His symptoms subsided spontaneously over the next few days and he was discharged uneventfully. Anti-parvovirus IgM titer was elevated during hospitalization and typical erythema infectiosum was seen approximately 1 week after discharge. During 6 months follow-up, he remained stable without recurrence of a hemorrhagic episode. Finally, we concluded that his cephalhematoma was responsible for acute parvoviral infection. This is believed to be the first report describing a possible association between parvovirus B19 infection and cephalhematoma. Parvovirus B19 infection should be considered in the differential diagnosis of children who present with unexplained hemorrhage such as cephalhematoma or petechiae.

Drug rash with eosinophilia and systemic symptoms syndrome associated with use of phenytoin, divalproex sodium, and phenobarbital.

Science.gov (United States)

Brizendine, Christina E; Naik, Paras J

2013-03-15

A probable case of drug reaction with eosinophilia and systemic symptoms (DRESS) associated with consecutive use of three medications for seizure control is reported. A 36-year-old woman was treated at a community hospital for a mild fever (37.9°C) and diffuse raised maculopapular rash with erythema. Three weeks previously, she had been diagnosed with a seizure disorder and initiated on phenytoin (dose unknown) at that time; about two weeks later, she developed a rash, prompting a switch from phenytoin to extended-release divalproex sodium 250 mg orally twice daily. During the week after discontinuation of phenytoin, the rash was improving, but about five days after the initiation of divalproex therapy, she had worsening rash and pruritus requiring urgent treatment; the divalproex was discontinued, and phenobarbital 30 mg three times daily was initiated for continued seizure control. Despite the discontinuation of phenytoin and divalproex, the patient's hepatic function worsened over five days, and phenobarbital therapy was discontinued. With continued deterioration of the patient's condition to fulminant hepatic failure, a transfer to a liver transplant facility was arranged. The use of the adverse reaction probability scale of Naranjo et al. in this case yielded a score of 8, indicating a probable relationship between DRESS and the serial use of phenytoin, divalproex, and phenobarbital. After receiving phenytoin for treatment of seizure disorder, a 36-year-old woman developed a fever and maculopapular rash with erythema. This reaction continued even after drug therapy was switched to extended-release divalproex and then phenobarbital. The patient's liver function deteriorated despite discontinuation of all seizure medications.

The impact of a Wastewater Treatment Works in Southern Gauteng, South Africa on efavirenz and nevirapine discharges into the aquatic environment

Directory of Open Access Journals (Sweden)

C. Schoeman

2017-06-01

Although an order of magnitude lower nevirapine concentrations displayed the opposite behaviour and gradually increased through the various stages of purification in the WWTP. Minor fluctuations occurred but the concentrations of nevirapine were higher at the effluent (between 92 and 473 ng/L than those entering the WWTP. No nevirapine was detected in the PST sludge. The increase in nevirapine concentrations are likely to be the result of the de-conjugation of the hydroxylated metabolites of nevirapine in the WWTP, its resistance to degradation and the lack of binding of the nevirapine to the PST sludge.

Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

OpenAIRE

Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

2014-01-01

Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

Good performance of an immunoassay based method for nevirapine measurements in human breast milk

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Persson Theilgaard, Zahra; Chiduo, Mercy

2011-01-01

, developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated...

Electrochemical studies of nevirapine, an anti-HIV drug, and its assay in tablets and biological samples

Directory of Open Access Journals (Sweden)

JALDAPPAGARI SEETHARAMAPPA

2012-06-01

Full Text Available The electrochemical oxidation of nevirapine, an anti-HIV drug, at a glassy carbon electrode has been studied by voltammetric techniques. Nevirapine showed one well defined irreversible oxidation peak with a potential of 0.749 V in phosphate buffer at pH 10. The effects of different electrolytes, pH and scan rate on the electrochemical behaviour of nevira¬pine were examined to determine the optimum reaction conditions. The oxidation peak current was found to vary linearly with the concentration of nevirapine in the range of 5.0 – 350 µM. The limit of detection and limit of quantification values were calculated and found to be 1.026 µM and 3.420 µM, respectively. The low relative standard deviation values of inter-day and intra-day assays highlighted the good reproducibility of the proposed m¬ethod for assay of nevirapine. Further, a sensitive and accurate differential pulse voltammetric method was developed for the determination of nevirapine concentrations in pharma¬ceutical formulations.

High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

Directory of Open Access Journals (Sweden)

Sehgal S

2008-01-01

Full Text Available In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25 of the children while mutation T215Y was found in none. Two of the six drug naοve children also showed K103N mutation. Thus, Indian children drug naοve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

Directory of Open Access Journals (Sweden)

Ashley R. Longstreet

2013-11-01

Full Text Available 2-Chloro-3-amino-4-picoline (CAPIC is a strategic building block for the preparation of nevirapine, a widely-prescribed non-nucleosidic reverse transcriptase inhibitor for the treatment of HIV-infected patients. A continuous synthesis to the bromo derivative of a CAPIC intermediate, 2-bromo-4-methylnicotinonitrile, that terminates in a dead-end crystallization is described. The route uses inexpensive, acyclic commodity-based raw materials and has the potential to enable lower cost production of nevirapine as well as other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process.

HIV and pregnancy: Maternal and neonatal evolution

Directory of Open Access Journals (Sweden)

Diego Cecchini

2011-10-01

Full Text Available Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006. Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median: 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55% or a protease inhibitor (32%]. Overall incidence of toxicity was 12.5%: rash (8%, anemia (3.5% and hepatotoxicity (1%. Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. Twenty six percent had obstetric complications and 16% had preterm delivery. Of the newborns, 1.6% had congenital defects and 9% had neonatal complications. Overall neonatal mortality was 1% and perinatal transmission was 0.7%. Protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. In our population, hepatotoxicity was low despite frequent use of nevirapine. Protease inhibitor use was associated to preterm delivery. A favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events.

Ron Rash: One Foot in Eden

DEFF Research Database (Denmark)

Bjerre, Thomas Ærvold

2010-01-01

An analysis of Ron Rash's novel One Foot in Eden, focusing on his attachment to place and his depiction of the internal conflicts between farmers and townspeople in a small Appalachian community. Rash depicts the contemporary Southerner’s struggle to maintain his or her roots in a time of rapid...

Evaluating the febrile patient with a rash.

Science.gov (United States)

McKinnon, H D; Howard, T

2000-08-15

The differential diagnosis for febrile patients with a rash is extensive. Diseases that present with fever and rash are usually classified according to the morphology of the primary lesion. Rashes can be categorized as maculopapular (centrally and peripherally distributed), petechial, diffusely erythematous with desquamation, vesiculobullous-pustular and nodular. Potential causes include viruses, bacteria, spirochetes, rickettsiae, medications and rheumatologic diseases. A thorough history and a careful physical examination are essential to making a correct diagnosis. Although laboratory studies can be useful in confirming the diagnosis, test results often are not available immediately. Because the severity of these illnesses can vary from minor (roseola) to life-threatening (meningococcemia), the family physician must make prompt management decisions regarding empiric therapy. Hospitalization, isolation and antimicrobial therapy often must be considered when a patient presents with fever and a rash.

Drug Rash with Eosinophilia and Systemic Symptoms: Two Emergency Department Cases

OpenAIRE

Tsyrulnik, Alina; Landman, Adam B.

2011-01-01

Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug event that appears with a generalized rash, fevers, and dysfunction of 1 or more organ systems. We describe 2 patients (1 adult and 1 pediatric) seen in the emergency department with DRESS, and review the clinical presentations, potential complications, and management of DRESS. Although rare, it can be associated with significant morbidity, including liver failure and death, and should be considered in th...

Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

Science.gov (United States)

Kakande, Betty; Isaacs, Thuraya; Muloiwa, Rudzani; Dlamini, Sipho; Lehloenya, Rannakoe

2015-01-01

A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm (3) in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

Transverse myelitis associated with an itchy rash and hyperckemia: neuromyelitis optica associated with dermatitis herpetiformis.

Science.gov (United States)

Iyer, Anand; Rathnasabapathi, Devipriya; Elsone, Liene; Mutch, Kerry; Terlizzo, Monica; Footitt, David; Jacob, Anu

2014-05-01

Neuromyelitis optica is associated with severe neurodisability if not recognized and treated promptly. Several autoimmune disorders are associated with this condition and may vary in their presentation. It is essential that clinicians are aware of the uncommon presenting features of neuromyelitis optica and associated autoimmune conditions. A 53-year-old woman presented with nausea and vomiting and was noted to have an asymptomatic elevated creatinine kinase level, which improved with conservative management. She had a history of iron-deficiency anemia due to long-standing celiac disease that was managed with a gluten-free diet. She then presented with recurrent transverse myelitis and a vesicobullous rash over her arms and feet that was pruritic and excoriating. Skin biopsy results confirmed a clinical diagnosis of dermatitis herpetiformis and antibody test findings against aquaporin-4 were positive, leading to a diagnosis of neuromyelitis optica spectrum disorder. She was treated with methylprednisolone sodium succinate, plasma exchange, and azathioprine and has remained in remission. This report highlights the association of neuromyelitis optica with dermatitis herpetiformis, which can present even without clinical features of celiac disease. Nausea, vomiting, and asymptomatic hyperCKemia should be recognized as rare presenting features of neuromyelitis optica.

Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine

NARCIS (Netherlands)

Negredo, Eugenia; Ribalta, Josep; Paredes, Roger; Ferré, Raimón; Sirera, Guillem; Ruiz, Lidia; Salazar, Juliana; Reiss, Peter; Masana, Lluís; Clotet, Bonaventura

2002-01-01

Background: The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity. Objective: To assess the

Antibiotic-Induced Rash in Patients With Infectious Mononucleosis.

Science.gov (United States)

Thompson, Dennis F; Ramos, Carroll L

2017-02-01

To provide an extensive review of case reports, epidemiological data, and the underlying mechanism of antibiotic-induced skin rash in patients with concurrent infectious mononucleosis (IM). A MEDLINE literature search inclusive of the dates 1946 to June 2016 was performed using the search terms anti-bacterial agents and infectious mononucleosis. EMBASE (1980 to June 2016) was searched using the terms mononucleosis and antibiotic agent and drug eruption. References of all relevant articles were reviewed for additional citations and information. We selected English-language, primary literature, review articles, and mechanistic articles that addressed antibiotic-induced skin rash in patients with concurrent IM. We assessed all case reports available for causality utilizing a modified Naranjo nomogram specifically designed for this subject. We assembled the available epidemiological data into tables to identify trends in incidence rates over the years. We identified 17 case reports of antibiotic-associated rash in patients with IM. The median Naranjo score was 6 (range = 1 to 8). The top 3 reported drugs were ampicillin, azithromycin, and amoxicillin. Incidence of this adverse effect was higher in the 1960s (55.6%, 45%, and 33%) than in 2013 (33% and 15%). The mechanism most commonly proposed is a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic. A reassessment of the long-held belief of the high incidence (80%-100%) of antibiotic-induced skin rash in patients with IM seems prudent. Additional studies will be necessary to clarify this issue.

Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

DEFF Research Database (Denmark)

Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

2017-01-01

Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is...

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Directory of Open Access Journals (Sweden)

Sinha Sanjeev

2011-11-01

Full Text Available Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV and tuberculosis (TB co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART when co-administered with rifampicin-containing antituberculosis treatment (ATT and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1% patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83 at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10, 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08, 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10 respectively and 3.04 μg/ml (in cases. Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in

Validity of genito-urinary discharges, genital ulcers and genital rashes as indicators of seroincident HSV-2 infection

Directory of Open Access Journals (Sweden)

Eziyi Iche Kalu

2015-06-01

Full Text Available Objective: To evaluate the validity of vaginal discharges, urethral discharges, genital rashes, and painful genital ulcers as indicators of early detection of incident herpes simplex virus type 2 (HSV-2 infection among pregnant women in Benin metropolis. Methods: Participants were antenatal clinic attendees of University of Benin Teaching Hospital and Central Hospital, Benin. Baseline sociodemographic, obstetric and HSV-2 serological data were collected. The HSV-2-seronegative returned for a repeat HSV-2 antibody assay before delivery date. Data on incidence of genital rashes, abnormal vaginal discharges, painful genital ulcers and urethral discharges were collected. Results: The sensitivities of abnormal vaginal discharges, genital rashes, urethral discharges and painful genital ulcers were 82.3%, 70.6%, 41.2% and 28.6% respectively; while their positive-predictive values were 53.8%, 60.0%, 58.3% and 66.7% respective. All the symptoms had >95% specificities and 95% negative-predictive values for seroincident HSV-2 infection. Conclusions: Abnormal vaginal discharge, genital rashes, urethral discharges and genital ulcers are valid indicators of seroincident HSV-2 infection and could be useful in formulation of screening tools in resource-limited settings.

Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children

NARCIS (Netherlands)

Bienczak, A.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Walker, A.S.; Owen, A.; Gibb, D.M.; Burger, D.M.; McIlleron, H.; Denti, P.

2017-01-01

OBJECTIVES: To characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children. METHODS: Non-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children

Red, Itchy Rash? Get the Skinny on Dermatitis

Science.gov (United States)

... Subscribe April 2012 Print this issue Red, Itchy Rash? Get the Skinny on Dermatitis En español Send us your comments You’ve probably had a rash at some point or another, whether from poison ...

A non-travel related rash in a traveler

Directory of Open Access Journals (Sweden)

Keith A. Sacco

2017-01-01

Full Text Available A 45-year-old man was admitted for investigation of a symmetric lower limb rash associated with recurrent fever for two weeks following a hiking trip in Italy and Greece. He was treated for sepsis secondary to lower limb cellulitis with no clinical improvement and subsequently diagnosed with Streptococcus gallolyticus endocarditis mediating an infectious vasculitis.

A Rejang River rash

Directory of Open Access Journals (Sweden)

Jean-Li Lim

2014-04-01

Full Text Available A 30-year-old Iban woman presented to a rural primary healthcare clinic located along the Batang Rejang in Sarawak. She had a 2-day history of rash, which started over her trunk and later spread to her face and limbs. What started out as individual erythematous maculopapular spots later coalesced to form larger raised blotches. The rash was extremely pruritic and affected her sleep, and hence her visit. The rash was preceded by high grade, persistent fever that was temporarily relieved by paracetamol. She also complained of malaise, arthralgia and myalgia. Her appetite had been poor since the onset of the fever. She lived in a long house at the edge of the jungle. Although she did not have a history of going into the jungle to forage, she went regularly to the river to wash clothes. Clinically, she appeared lethargic and had bilateral conjunctival injection. Her left anterior cervical lymph nodes were palpable. There were erythematous macules measuring 5 to 15 mm distributed over her whole body but predominantly over the chest and abdominal region (Figure 1. An unusual skin lesion was discovered at the right hypochondriac region. This lesion resembled a cigarette burn with a necrotic centre (Figure 2. There was no evidence of hepato-splenomegaly. Examination of the other systems was unremarkable. On further questioning, the patient admitted being bitten by a ‘kutu babi’ or mite 3 days before the onset of her fever.

Rashes: The Itchy Truth

Science.gov (United States)

... while it's healing. Allergic contact dermatitis is a rash caused by contact with an allergen (say: AL-ur-jun). An ... when you'll be going outside. For allergic dermatitis or irritant contact dermatitis, try to avoid that substance. If you ...

Rash caused by Oryctes nasicornis.

Science.gov (United States)

Veraldi, Stefano; Fanoni, Daniele; Nazzaro, Gianluca

2016-02-01

We report a case of rash caused by crushing of a male of Oryctes nasicornis (Linnaeus 1758) (Coleoptera, "http:// it. wikipedia. org/ wiki/ Scarabaeidae" \\o "Scarabaeidae" Scarabaeidae), popularly known as "European rhinoceros beetle", on the skin of an Italian tourist who developed the reaction during a trip to Turkey. The rash appeared one hour after the crushing of the insect on the skin. The patient was observed one day later, when she returned to Italy. To our knowledge, no similar cases have been reported in the literature. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

Hepatic adverse events during highly active antiretroviral therapy containing nevirapine: a case report

Directory of Open Access Journals (Sweden)

Yamazhan Tansu

2002-09-01

Full Text Available Abstract Background Hepatotoxicity is one of the most serious complications of highly active antiretroviral therapy (HAART. The aim of this report is to analyse an HIV infected patient on HAART including nevirapine and taking antidepressive agents, with acute toxic hepatitis. Case presentation A 39 year old patient diagnosed as HIV positive one month ago administered to the clinical ward of the Department of Infectious Diseases and Clinical Microbiology in Ege University Medical School with high fever, malaise, nausea, diarrheae and elevated liver enzymes (ALT 1558 U/L, AST 4288 U/L. He has been using HAART including zidovudine+lamivudine (2 × 1/day and nevirapine (2 × 200 mg/day, following dose escalation for 22 days, sertralin and diazepam for 12 days and lithium for 10 days. The patient was hospitalized. Antiretroviral and antidepressant treatments were stopped. The day after admission, his fever dropped and his symptoms improved. Clinical improvement continued on the following days. The patient was discharged upon his request on the 14th day of hospitalization. The liver function tests returned to normal levels in two weeks following discharge. Conclusion Close monitoring of liver enzymes during the first 12 weeks of nevirapine therapy is critical to prevent life threatening events.

Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

Science.gov (United States)

Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

2015-05-25

The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (pbiotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Recognising haemorrhagic rash in children with fever: a survey of parents' knowledge.

Science.gov (United States)

Aurel, M; Dubos, F; Motte, B; Pruvost, I; Leclerc, F; Martinot, A

2011-07-01

Early recognition and treatment of meningococcal disease improves its outcome. Haemorrhagic rash is one of the most specific signs that parents can learn to recognise. To determine the percentage of parents able to recognise a haemorrhagic rash and perform the tumbler test. 123 parents of children consulting for mild injuries were interviewed about the significance and recognition of haemorrhagic rash in febrile children. Although 88% of parents undressed their children when they were febrile, it was never to look specifically for a skin rash. Only 7% (95% CI 3% to 12%) were able to recognise a petechial rash and knew the tumbler test. Information campaigns about the significance of haemorrhagic rash and about the tumbler test are needed.

Oxcarbazepine Induced Maculopapular Rash - A Case Report

OpenAIRE

Biswas, Arunava; Mitra, Ritabrata; Sen, Sukanta; Pal, Agnik; Tripathi, Santanu Kumar

2015-01-01

Unlike carbamazepine, newer anti epileptic drug like oxcarbazepine, reports fewer side effects. In this report we describe a case of oxcarbazepine induced maculopapular rash probably happened because of a drug interaction with isoniazid, and a brief review of the existing literature is presented herewith. A 40-year-old male patient received oxcarbazepine 300mg twice daily along with other anti-tubercular drugs including isoniazid (300mg) once daily since two days. Extensive cutaneous rash wit...

Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique

NARCIS (Netherlands)

Lamorde, M.; Fillekes, Q.; Sigaloff, K.; Kityo, C.; Buzibye, A.; Kayiwa, J.; Merry, C.; Nakatudde-Katumba, L.; Burger, D.M.; Wit, T.F. de

2014-01-01

BACKGROUND: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations

Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique

NARCIS (Netherlands)

Lamorde, Mohammed; Fillekes, Quirine; Sigaloff, Kim; Kityo, Cissy; Buzibye, Allan; Kayiwa, Joshua; Merry, Concepta; Nakatudde-Katumba, Lillian; Burger, David; Rinke de Wit, Tobias F.

2014-01-01

In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma

a study of nevirapine toxicity in hiv infected pregnant women

African Journals Online (AJOL)

Esem

HIV infected women commenced on nevirapine-based regimen in the current pregnancy with CD4 counts up to. 3. 350 cells/mm at the University Teaching Hospital,. Lusaka, Zambia. Design: Longitudinal observational study with 2 arms. Group 1 (low CD4 count arm): HIV infected pregnant. 3 women with CD4 counts less ...

Erlotinib-induced rash spares previously irradiated skin

International Nuclear Information System (INIS)

Lips, Irene M.; Vonk, Ernest J.A.; Koster, Mariska E.Y.; Houwing, Ronald H.

2011-01-01

Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed. (orig.)

Skin rash in patients treated with neoadjuvant erlotinib (Tarceva in resectable non-small cell lung cancer: Predictor for tumor response and survival?

Directory of Open Access Journals (Sweden)

Van Gool MH

2017-08-01

Full Text Available Background: Skin rash during treatment with epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKI has been reported to be predictive for response and survival in patients with advanced non-small cell lung cancer (NSCLC. The aim of this analysis was to evaluate whether skin rash during treatment (as a biomarker in a preoperative setting was related to response and survival. Methods: This study was designed as an open-label phase II trial (also known as M06NEL. Patients received preoperative erlotinib (Tarceva 150 mg once daily for 3 weeks. Skin toxicity during treatment was analysed in relation to metabolic and histopathological response, overall survival (OS and progression-free survival (PFS. Results: In total 59 patients (25 male, 34 female were eligible for analysis. In 39 patients (66% skin toxicity occurred. According to National Cancer Institute Common Toxicity Criteria (NCICTC, Grade 1 toxicity was seen in 15 patients (25%, Grade 2 in 19 patients (32% and Grade 3 in five patients (8%. None of the patients showed skin toxicity Grade 4 and 5. The median follow up was 74 months. Thirty-six patients (61% were alive at time of analysis. Twenty-seven patients (46% showed disease progression during follow up. Hazard ratios (HR indicated lower risk of death (HR = 0.66, 95%CI: 0.29 - 1.50 and progression (HR = 0.64, 0.30 - 1.36, although in this small group results were not significant. Skin rash did not adequately predict response. Conclusions: In this neoadjuvant setting with limited treatment time in patients with early stage NSCLC, skin rash was not associated with response and survival and cannot be used as an early biomarker.

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

Science.gov (United States)

Montaner, J S; Reiss, P; Cooper, D; Vella, S; Harris, M; Conway, B; Wainberg, M A; Smith, D; Robinson, P; Hall, D; Myers, M; Lange, J M

1998-03-25

Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. Double-blind, controlled, randomized trial. University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. Plasma HIV-1 RNA. Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death

Rilpivirine exposure in plasma and sanctuary site compartments after switching from nevirapine-containing combined antiretroviral therapy.

Science.gov (United States)

Mora-Peris, Borja; Watson, Victoria; Vera, Jaime H; Weston, Rosy; Waldman, Adam D; Kaye, Steve; Khoo, Saye; Mackie, Nicola E; Back, David; Winston, Alan

2014-06-01

Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine. HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively). Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90. Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Poison ivy - oak - sumac rash

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/000027.htm Poison ivy - oak - sumac rash To use the sharing features on this page, please enable JavaScript. Poison ivy, oak, and sumac are plants that commonly ...

Antioxidant modulation of nevirapine induced hepatotoxicity in rats

Directory of Open Access Journals (Sweden)

Awodele Olufunsho

2015-03-01

Full Text Available HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART. However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day, vitamin C (8 mg/kg/day, vitamin E (5 mg/kg/day and/or NVP (6 mg/kg/day for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05 elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05 higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05 lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05 higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05 higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda

NARCIS (Netherlands)

Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-01-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected

A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

DEFF Research Database (Denmark)

Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy

2011-01-01

Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated...... in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI...... = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure...

Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

Directory of Open Access Journals (Sweden)

Sanjiv M Baxi

Full Text Available Effective antiretroviral (ARV therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%. We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits. Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3% and increased in higher quartiles (to 158/204 (77.5% for quartile 4. The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001 those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.

Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy. [version 1; referees: 1 approved, 2 approved with reservations

Directory of Open Access Journals (Sweden)

Betty Kakande

2015-06-01

Full Text Available A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz.   Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

RASH D - A mercury programme for neutron shielding calculations

International Nuclear Information System (INIS)

Bendall, D.E.

1962-08-01

An improved version of an earlier neutron shielding programme (RASH B) is described. The new programme is also written in Mercury Autocode and solves a set of multigroup diffusion equations in one dimension. It differs from RASH B in that distributed source terms may be introduced into all the groups if required. Some other improvements are also included. (author)

Ibrutinib-associated skin toxicity: a case of maculopapular rash in a 79-year old Caucasian male patient with relapsed Waldenstrom’s macroglobulinemia and review of the literature

Directory of Open Access Journals (Sweden)

Anders Bisgaard Jensen

2017-04-01

Full Text Available Waldenstrom's macroglobulinamia (WM is a rare malignant lymphoproliferative disorder, characterized by monoclonal IgM paraproteinemia and neoplastic proliferation of malignant lymphoplasmacytoid cells in the bone marrow. Traditionally, WM has been treated with modalities similar to those used in the management of other indolent lymphomas. Just recently, based on impressive clinical trial results in heavily pretreated WM patients, a new Bruton Tyrosine Kinase-inhibitor, Ibrutinib, has been approved for the treatment of this disorder. As the use of Ibrutinib in WM outside clinical trials is still limited, only few clinical reports illustrating treatment side effects are currently available. Here we review the current literature specific on Ibrutinib-associated rash in hematologic patients, and report on an elderly patient with WM, who developed a red maculopapular non-pruritic rash 12 weeks after starting Ibrutinib therapy. Without modifications of the ongoing Ibrutinib schedule, the rash regressed within two weeks of treatment with topical steroidcontaining dermatological compounds.

Shampoo-clay heals diaper rash faster than calendula officinalis.

Science.gov (United States)

Adib-Hajbaghery, Mohsen; Mahmoudi, Mansoreh; Mashaiekhi, Mahdi

2014-06-01

Diaper rash is one of the most common skin disorders of infancy and childhood. Some studies have shown that Shampoo-clay was effective to treat chronic dermatitis. Then, it is supposed that it may be effective in diaper rash; however, no published studies were found in this regard. This study aimed to compare the effects of Shampoo-clay (S.C) and Calendula officinalis (C.O) to improve infantile diaper rash. A randomized, double blind, parallel controlled, non-inferiority trial was conducted on 60 outpatient infants referred to health care centers or pediatric clinics in Khomein city and diagnosed with diaper rash. Patients were randomly assigned into two treatment groups including S.C group (n = 30) and C.O group (n = 30) by using one to one allocation ratio. The rate of complete recovery in three days was the primary outcome. Data was collected using a checklist and analyzed using t-test, Chi-square and Fisher's exact tests and risk ratio. Totally, 93.3% of lesions in the S.C group healed in the first 6 hours, while this rate was 40% in C.O group (P < 0.001). The healing ratio for improvement in the first 6 hours was 7 times more in the S.C group. In addition, 90% of infants in the SC group and 36.7% in the C.O group were improved completely in the first 3 days (P < 0.001). S.C was effective to heal diaper rash, and also had faster effects compared to C.O.

Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

Science.gov (United States)

Kamijima, Michihiro; Wang, Hailan; Yamanoshita, Osamu; Ito, Yuki; Xia, Lihua; Yanagiba, Yukie; Chen, Cishan; Okamura, Ai; Huang, Zhenlie; Qiu, Xinxiang; Song, Xiangrong; Cai, Tingfeng; Liu, Lili; Ge, Yichen; Deng, Yingyu; Naito, Hisao; Yoshikawa, Tetsushi; Tohyama, Mikiko; Li, Laiyu; Huang, Hanlin; Nakajima, Tamie

2013-12-01

Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz.

Science.gov (United States)

Llibre, J M; Santos, J R; Puig, T; Moltó, J; Ruiz, L; Paredes, R; Clotet, B

2008-11-01

To evaluate the expected activity of etravirine in clinical samples, according to mutational patterns associated with decreased virological response (VR). We identified 1586 routine clinical samples with resistance-associated mutations (RAMs) to nevirapine and efavirenz (K103N 60%, Y181C 37%, G190A 27%, V108I 13%). Concerning in vitro identified etravirine mutations, samples with F227C, Y181I, M230L or L100I plus K103N plus Y181C were considered highly resistant. Samples with two RAMs plus Y181C or V179D or K101E or Y188L were considered intermediate. The prevalence of 13 RAMs recently associated with decreased VR to etravirine in the DUET clinical trials was also investigated. Most samples (69%) harboured more than one IAS-USA RAM to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): 42% harboured two RAMs, 21% three RAMs and 6% four or more RAMs. The prevalence of 13 specific etravirine RAMs was V179F 0.12%, G190S 3.9%, Y181V 0.1%, V106I 2.6%, V179D 1.6%, K101P 2.0%, K101E 10.1%, Y181C 36.9%, A98G 5.9%, V90I 6.9%, Y181I 3.6%, G190A 27% and L100I 9.1%. The five RAMs with the most impact on VR (V179F/D, G190S, Y181V and V106I) occurred less often. Overall, 8.2% of the samples had three or more etravirine RAMs and only 1.1% had four or more. In addition, patterns of RAMs previously associated with intermediate etravirine resistance were present in 26.2% of the samples, whereas 4.85% displayed patterns of high-degree resistance. For RAMs associated with decreased VR, etravirine resistance in routine clinical samples was lower than previously reported. High-degree resistance was uncommon, even in patients with resistance to first-generation NNRTIs, whereas low-to-intermediate etravirine resistance was more common.

Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine

NARCIS (Netherlands)

Conway, B.; Wainberg, M. A.; Hall, D.; Harris, M.; Reiss, P.; Cooper, D.; Vella, S.; Curry, R.; Robinson, P.; Lange, J. M.; Montaner, J. S.

2001-01-01

OBJECTIVE: To evaluate the development of phenotypic and genotypic resistance to zidovudine, didanosine and nevirapine as a function of the virologic response to therapy in a group of drug-naive individuals receiving various combinations of these agents. DESIGN: All patients were enrolled in a

A New Validated RP- HPLC Method for the Determination of Nevirapine in Human Plasma

Directory of Open Access Journals (Sweden)

C. H. Venkata Kumar

2010-01-01

Full Text Available A rapid, selective and sensitive high performance liquid chromatographic method for the estimation of nevirapine in human plasma has been developed. Chromatography was carried out on a Hypersil BDS C18 column using a mixture of ammonium acetate buffer (pH 4.0 ± 0.05 and acetonitrile (85:15 v/v as the mobile phase. The eluents were monitored for the drug by UV detection at 254 nm. Oxcarbazepine was used as an internal standard for this study. The retention times for nevirapine and oxcarbazepine were found to be 7.2 and 14.7 min respectively. The method was found to be linear in the concentration range of 50 ng/mL to 5003.7 ng/mL. The method was validated as per FDA guidelines and was found to be suitable for bioequivalence and pharmacokinetic studies.

Rash, disseminated intravascular coagulation and legionella: Episode 10 and a rewind into the past

Directory of Open Access Journals (Sweden)

Prashanth M. Thalanayar

2015-01-01

Full Text Available Legionella pneumophila is the most common cause of legionellosis and is one of the organisms causing atypical pneumonia. We report the presentation of disseminated intravascular coagulation (DIC and skin rash in a single case of severe Legionella pneumonia. The unique clinical presentation of a diffuse rash diagnosed as purpura fulminans and the unpredictable variations encountered during the diagnostic work-up of the case make this write-up crucial. This article synthesizes all reported cases of L. pneumonia associated with cutaneous manifestations as well as cases presenting with DIC. Furthermore, this manuscript illustrates the correlation between cutaneous and coagulopathic manifestations, and morbidity and mortality from L. pneumonia.

Oxcarbazepine induced maculopapular rash - a case report.

Science.gov (United States)

Biswas, Arunava; Mitra, Ritabrata; Sen, Sukanta; Pal, Agnik; Tripathi, Santanu Kumar

2015-01-01

Unlike carbamazepine, newer anti epileptic drug like oxcarbazepine, reports fewer side effects. In this report we describe a case of oxcarbazepine induced maculopapular rash probably happened because of a drug interaction with isoniazid, and a brief review of the existing literature is presented herewith. A 40-year-old male patient received oxcarbazepine 300mg twice daily along with other anti-tubercular drugs including isoniazid (300mg) once daily since two days. Extensive cutaneous rash with intense itching developed which subsided on discontinuation of oxcarbazepine. This case highlights the fact that there is a potential possibility of drug-drug interaction between oxcarbazepine and isoniazid and concomitant use of these two drugs should better be avoided during clinical practice.

Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: The XXXX experience

Science.gov (United States)

Bar-Ad, Voichita; Zhang, Qiang (Ed); Harari, Paul M.; Axelrod, Rita; Rosenthal, David I.; Trotti, Andy; Jones, Christopher U.; Garden, Adam S.; Song, Guobin; Foote, Robert L.; Raben, David; Shenouda, George; Spencer, Sharon A.; Harris, Jonathan; Le, Quynh-Thu

2016-01-01

Purpose The purpose of the present study was to evaluate severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy and cetuximab. Materials & Methods Analysis included patients who received loading dose and ≥ 1cetuximab dose concurrent with definitive chemoradiotherapy (70Gy + cisplatin) or postoperative chemoradiotherapy (60–66Gy + docetaxel or cisplatin). Results Six hundred two patients were analyzed; 383 (63.6%) developed Grade 2–4 cetuximab rash. Patients manifesting Grade 2–4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were more likely to be males (p=0.04), and had p16-negative (p=0.04) oropharyngeal tumors (p=0.003). In univariate analysis, Grade 2–4 rash was associated with better overall survival (OS) (hazard ratio [HR] 0.58, p<0.001) and progression-free survival (PFS) (HR 0.75, p=0.02), and reduced distant metastasis (DM) rate (HR 0.61, p=0.03), but not local-regional failure (LRF) (HR 0.79, p=0.16) relative to Grade 0–1 rash. In multivariable analysis, HRs for OS, PFS, DM, and LRF were 0.68 (p=0.008), 0.85 (p=0.21), 0.64 (p=0.06), and 0.89 (p=0.48). Grade ≥2 rash was associated with improved survival in p16 negative patients (HR 0.28 (0.11–0.74)) but not in p16 positive patients (HR 1.10 (0.42–2.89)) (p=0.05 for interaction). Twenty-five percent of patients with Grade 2–4 acute in-field radiation dermatitis experienced Grade 2–4 late skin fibrosis vs. 14% of patients with Grade 0–1 acute in-field radiation dermatitis (p=0.002). Conclusion Grade 2–4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2–4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2–4 skin fibrosis. PMID:27212198

Lamotrigine rechallenge after a skin rash. A combined study of open cases and a meta-analysis.

Science.gov (United States)

Serrani Azcurra, Daniel J L

2013-01-01

To determine the safety of lamotrigine rechallenge after a first episode of skin rash in bipolar patients. An open cases prospective study was conducted with patients who, developed a skin rash when first treated with lamotrigine, were refractory to other treatments, and were offered lamotrigine rechallenge using a different dose titration. Additionally a review was performed on previous skin rash management strategies and lamotrigine rechallenge reports. Every 3 out of 10 lamotrigine rechallenge patients required drug interruption due to persistent rash. One of them was potentially serious and resolved by stopping the lamotrigine. The review of available literature identified several lamotrigine rechallenge studies with rates of positive results varying between 70% and 87% depending on the study. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis after rechallenge. The rate of rash was higher when rechallenge began between 4 weeks from initial rash (19% vs. 7%, P=.001) and decreased when first rash showed no potentially serious signs (0% vs.19%, P=.01). Rechallenge is a viable option after a benign lamotrigine-induced rash, and can even be rechallenged after rash with greater precautions when there exists one or two potentially serious signs. In cases of more serious rash there are no reliable data available on rechallenge safety and it may pose a significant risk. In those cases rechallenge should better be avoided between 4 weeks from first rash. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).

Science.gov (United States)

Molins, Claudia R; Ashton, Laura V; Wormser, Gary P; Andre, Barbara G; Hess, Ann M; Delorey, Mark J; Pilgard, Mark A; Johnson, Barbara J; Webb, Kristofor; Islam, M Nurul; Pegalajar-Jurado, Adoracion; Molla, Irida; Jewett, Mollie W; Belisle, John T

2017-08-16

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N -acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

Science.gov (United States)

Onwuamah, Chika K; Ezechi, Oliver C; Herbertson, Ebiere C; Audu, Rosemary A; Ujah, Innocent A O; Odeigah, Peter G C

2014-01-01

Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

Directory of Open Access Journals (Sweden)

Chika K Onwuamah

Full Text Available Health concerns for HIV-infected persons on antiretroviral therapy (ART have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations.A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation.Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth.The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

Energy Technology Data Exchange (ETDEWEB)

Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu [Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Zhang, Qiang [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Harari, Paul M. [University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Axelrod, Rita [Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Rosenthal, David I. [University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Trotti, Andy [H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Jones, Christopher U. [Radiological Associates of Sacramento, Sacramento, California (United States); Garden, Adam S. [University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Song, Guobin [Virginia Mason Medical Center, Seattle, Washington (United States); Foote, Robert L. [Mayo Clinic, Rochester, Minnesota (United States); Raben, David [University of Colorado Comprehensive Cancer Center, Denver, Colorado (United States); Shenouda, George [McGill University, Montreal, Quebec (Canada); Spencer, Sharon A. [University of Alabama at Birmingham, Birmingham, Alabama (United States); Harris, Jonathan [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Stanford University Medical Center, Stanford, California (United States)

2016-08-01

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of

COMPARATIVE STUDY OF EFFICACY OF TWO ANTIRETROVIRAL REGIMENTS (ZIDOUVDINE+LAMIVUDINE+NEVIRAPHINE VS STAVUDINE+LAMIVUDINE+NEVIRAPINE IN HIV/AIDS PATIENTS

Directory of Open Access Journals (Sweden)

Mopuri Muneer Kanha

2015-02-01

Full Text Available BACKGROUND: AIDS, the acquired immunodeficiency syndrome, is the worst disease in the history of medicine due to HIV infection in many sexually active people. This disease is treated with two regimens of drugs in the ART centers at free of cost by the government. AIMS AND OBJECTIVES: To study and compare the efficacy of two antiretroviral regimens (zidovudine +lamivudine+ nevirapine vs ( S tavudine + lamivudine +nevirapine in HIV/AIDS patients. Methods: It is a longitudinal, prospective, observational study, carried at ART centers of siddhartha medical college, Vijayawada, AP and Guntur medical college, Guntur, AP from October 2006 to March 2008. Results: 650 patients were enrolled into study. Out of 650, 325 patients were received Tab.Zidovudine +Tab.Lamivudine+Tab.Nevirapine (Regimen A and 325 patients were received Tab. Stavudine + Tab.Lamivudine + Tab. Nevirapine (Regimen B in fixed drug combination. The study is designed for a Period of 12 months by recording observations at 0 months, 6months and 12months. All the cases enrolled had been studied prospectively at the ART centers and the data entered into the case sheets. The adherence to the ART is assessed by asking the patients to get the empty drug bottles and checking the number of remaining tablets. The chi - square test is applied for all the parameters after 6 months data and after 12 months data with degree of freedom (D f of > 1 = and > P = value as 0.05 (p=0.05 and the level of significance as x 2 >3.84. CONCLUSIONS: Stavudine containing regimen B is having better efficacy than zidovudine containing regimen A

Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India

Directory of Open Access Journals (Sweden)

Mini S Jacob

2011-01-01

Full Text Available Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP provided to delivering HIV seropositive (HIV+ve women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

Metabolic alkalosis secondary to baking soda treatment of a diaper rash.

Science.gov (United States)

Gonzalez, J; Hogg, R J

1981-06-01

A 4-month-old infant was seen with hypokalemic metabolic alkalosis that was associated with prior application of liberal amounts of sodium bicarbonate (baking soda) to a diaper rash. After exclusion of other etiologies of the infant's acid-base disturbance, a complete resolution occurred following discontinuation of the baking soda applications. This case report provides a reminder of the significant side effects that may result from the excessive use of a seemingly harmless household substance.

Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy G.

2015-01-01

and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine). Methods Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks...... postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant. Results HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median...... (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg...

Performance of HIV Prevention of Mother-To-Child Transmission Programs in Sub-Saharan Africa: Longitudinal Assessment of 64 Nevirapine-Based Programs Implemented in 25 Countries, 2000-2011.

Directory of Open Access Journals (Sweden)

Joël Ladner

Full Text Available To evaluate the performance and to identify predictive factors of performance in prevention of mother-to-child HIV transmission programs (PMTCT in sub-Saharan African countries.From 2000 to 2011, PMTCT programs included in the Viramune Donation Programme (VDP were prospectively followed. Each institution included in the VDP provided data on program implementation, type of management institution, number of PMTCT sites, key programs outputs (HIV counseling and testing, NVP regimens received by mothers and newborns. Nevirapine Coverage Ratio (NCR, defined as the number of women who should have received nevirapine (observed HIV prevalence x number of women in antenatal care, was used to measure performance. Included programs were followed every six months through progress reports.A total of 64 programs in 25 sub-Saharan African countries were included. The mean program follow-up was 48.0 months (SD = 24.5; 20,084,490 women attended in antenatal clinics were included. The overall mean NCR was 0.52 (SD = 0.25, with an increase from 0.37 to 0.57 between the first and last progress reports (p<.0001; NCR increased by 3.26% per year-program. Between the first and the last report, the number of women counseled and tested increased from 64.3% to 86.0% (p<.0001, the number of women post-counseled from 87.5% to 91.3% (p = 0.08. After mixed linear regression analysis, type of responsible institution, number of women attended in ANC, and program initiation in 2005-2006 were significant predictive factors associated with the NCR. The effect of the time period increased from earlier to later periods.A longitudinal assessment of large PMTCT programs shows that scaling-up of programs was increased in sub-Saharan African countries. The PMTCT coverage increased throughout the study period, especially after 2006. Performance may be better for programs with a small or medium number of women attended in ANC. Identification of factors that predict PMTCT program

Azithromycin-induced rash in a patient of infectious mononucleosis - a case report with review of literature.

Science.gov (United States)

Banerjee, Indranil; Mondal, Somnath; Sen, Sukanta; Tripathi, Santanu Kumar; Banerjee, Gautam

2014-08-01

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in 'probable' category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.

The “Pearls” of Multidisciplinary Team: Conquering the Uncommon Rosette Rash

Directory of Open Access Journals (Sweden)

Nitin Verma

2016-01-01

Full Text Available Linear IgA disease of childhood (LAD also known as chronic bullous disease of childhood is an autoimmune disease with IgA deposition at the basement membrane zone leading to a vesiculobullous rash. It has a clinical appearance which frequently is described as resembling “strings of pearls” or rosette-like. Diagnosis is usually clinical but sometimes biopsy is required. Dapsone is widely considered to be the first line therapy in the treatment of LAD. A 5-year-old girl presented with 4-day history of a widespread painful rash and pyrexia. The rash transformed into painful blisters. A recent contact with chickenpox was present. She remained apyrexial but hemodynamically stable and was treated as chickenpox patient with secondary infection. Due to persistent symptoms after repeated attendance she was reviewed by Dermatology team and diagnosed with linear IgA disease also known as chronic bullous disease of childhood. This was based on the presence of blistering rash with rosette appearance and string of pearl lesions. The clinical features of LAD can be difficult to distinguish from more common skin infections. Benefiting from the experience of other multidisciplinary teams can sometimes be a game changer and can lead to the correct diagnosis and treatment.

Clinical significance of skin rash in dengue fever: A focus on discomfort, complications, and disease outcome.

Science.gov (United States)

Huang, Hsin-Wei; Tseng, Han-Chi; Lee, Chih-Hung; Chuang, Hung-Yi; Lin, Shang-Hung

2016-07-01

To assess whether the cutaneous features in patients with dengue fever are associated with abnormal blood biochemistry, complications, and poor disease outcome. Forty five patients with dengue fever were identified at a medical center in Kaohsiung, Taiwan, from September to November 2014. All cases were exclusively caused by type 1 dengue virus. Patients were classified into two groups, based on the presence or absence of skin rash, and their rash was subclassified into maculopapular, morbilliform, and petechial types. Clinical symptoms, laboratory data, disease outcome, and complications were compared between the two groups. Thirty two patients with dengue fever developed skin rash (SP group, n = 32) while the rest of 13 did not (SN group, n = 13). The patient numbers in the maculopapular, morbilliform, and petechial group were 4, 21, and 7, respectively. The SP group was younger (P = 0.001), experienced more pruritus (P = 0.008) and more swollen palms/soles (P = 0.015) than the SN group. However, the SN group had greater genital mucosa involvement (P = 0.008), higher platelet transfusion rate (P = 0.003), and lower hemoglobin and hematocrit levels (P = 0.030) than the SP group. Patients with morbilliform lesions had a higher incidence of palm/sole swelling, less genital mucosal involvement, and a lower platelet transfusion rate than did patients with maculopapular or petechial lesions. Cutaneous manifestations provide an important clue to dengue fever. In patients with dengue fever, those with skin rash tend to have itching and swelling of the palms/soles, however, those without skin rash tend to have more complications and poor disease outcomes. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

DEFF Research Database (Denmark)

Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

2008-01-01

OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

Azithromycin-Induced Rash in a Patient of Infectious Mononucleosis – A Case Report with Review of Literature

Science.gov (United States)

Mondal, Somnath; Sen, Sukanta; Tripathi, Santanu Kumar; Banerjee, Gautam

2014-01-01

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in ‘probable’ category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare. PMID:25302218

Mononucleosis-like drug rash: An interesting case presentation

Directory of Open Access Journals (Sweden)

Reshma T Vishnani

2014-01-01

Full Text Available Dapsone hypersensitivity syndrome (DHS is a rare adverse effect of the commonly prescribed drug dapsone. We present a case of a 35-year-old male who was referred to us from the gastroenterologist with complaints of rash, nausea, vomiting, and jaundice since 2 days with a provisional differential diagnosis of infectious mononucleosis or viral exanthema. On enquiry patient gave history of taking dapsone a week prior for refractory urticaria. After thorough investigations we diagnosed him with DHS. This syndrome occurs in a relatively small proportion of patients, but it is associated with considerable morbidity and mortality. The reason for presenting this case is to remind physicians of the unpredictability and potential severity of this reaction which makes it a major concern in clinical practice.

Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

NARCIS (Netherlands)

Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.

2017-01-01

BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African

Possible hepatotoxic consequence of nevirapine use in juvenile albino rats

Directory of Open Access Journals (Sweden)

Elias Adikwu

2017-08-01

Full Text Available Context: Nevirapine (NVP is used in human immunodeficiency virus exposed neonates. This could present safety concern due to decreased liver metabolizing enzymes activity and renal clearance in neonates. Aims: To determine the hepatotoxic effect of NVP in juvenile albino rats. Methods: Juvenile albino rats were weighed, divided into groups and treated orally with 4-32 mg/kg/day of NVP for 14 days including a recovery group. The control groups were treated with water (placebo and normal saline (solvent. At the end of NVP treatment, rats were weighed and sacrificed, blood was collected and serum extracted. Serum was analyzed for alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, total bilirubin (TB and conjugated bilirubin (CB. The liver was harvested via dissection, weighed and evaluated for AST, ALT, ALP, superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, malondialdehyde (MDA levels and histological damage. Results: The body, absolute and relative liver weights of rats in NVP treated groups were not significantly different (p>0.05 when compared to placebo. However, serum levels of AST, ALT, ALP, TB and CB were significantly increased (p<0.05 in a dose-dependent manner in NVP-treated groups. Furthermore, liver levels of ALT, ALP, AST and MDA were significantly increased (p<0.05 while SOD, CAT, and GSH were decreased in a dose dependent manner in NVP-treated groups. NVP-treated rats were characterized by varying degrees of hepatic morphological alterations. However, in the recovery group, the effects of NVP were reversed. Conclusions: This study observed dose-dependent and reversible hepatotoxicity in nevirapine- treated juvenile albino rats.

Rash related to use of scented products. A questionnaire study in the Danish population. Is the problem increasing?

DEFF Research Database (Denmark)

Johansen, J D; Andersen, T F; Thomsen, L K

2000-01-01

. Further, it was determined whether risk of self-reported 1st-time rash from scented products had increased during the past 15 years compared to the preceding period. The sample consisted of 1537 persons, 801 female and 736 male, above the age of 15 years. The participants were interviewed person......-to-person to obtain a general health profile, and in this connection, questions were asked concerning rash related to the use of scented products. 28.6% (440/1537) had on some occasion experienced rash from scented products, 10.6% had experienced rash within the year prior to interview. A multivariate analysis showed...... that women had a significantly increased risk of reporting rash from scented products compared to men (odds ratio: 1.56, pyears had a significantly increased risk of reporting rash from scented products compared to older age groups...

Validation and clinical application of a method to quantify nevirapine in dried blood spots and dried breast-milk spots.

Science.gov (United States)

Olagunju, Adeniyi; Amara, Alieu; Waitt, Catriona; Else, Laura; Penchala, Sujan D; Bolaji, Oluseye; Soyinka, Julius; Siccardi, Marco; Back, David; Owen, Andrew; Khoo, Saye

2015-10-01

The validation and clinical application of an LC-MS/MS method for the quantification of nevirapine in dried blood spots (DBS) and dried breast-milk spots (DBMS) are presented. DBS and DBMS were prepared from 50 and 30 μL of nevirapine-spiked whole blood and human breast milk, respectively. Chromatographic separation was achieved on a reverse-phase C18 column with 0.1% formic acid in water/acetonitrile using a solvent gradient programme at a flow rate of 400 μL/min, and detection was by a TSQ Quantum Access triple quadrupole mass spectrometer. The clinical application was evaluated in HIV-positive nursing mothers and their breastfed infants. The assay was validated over the concentration range 50-10,000 ng/mL. Accuracy ranged from 93.3% to 113.4% and precision ranged from 1.9% to 12.0%. The mean (percentage coefficient of variation) recovery of nevirapine from DBS and DBMS was ≥ 70.7% (≤ 8.2) and the matrix effect was ≤ 1.04 (≤ 6.1). Nevirapine was stable in DBS and DBMS for ≥ 15 months at room temperature and -80°C. Mean (SD) AUC0-12, Cmax and Cmin in maternal plasma versus breast milk were 57,808 ng · h/mL (24,315) versus 55,817 ng · h/mL (22,368), 6140 ng/mL (2605) versus 5231 ng/mL (2215) and 4334 ng/mL (1880) versus 4342 ng/mL (2245), respectively. The milk-to-plasma concentration ratio over the dosing interval was 0.94 (0.15). Infant plasma concentrations 2 and 8 h after maternal dosing were 580.6 ng/mL (464.7-1607) and 584.1 ng/mL (381.5-1570), respectively. These methods further extend opportunities for conducting clinical pharmacokinetic studies in nursing mother-infant pairs, especially in resource-limited settings. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study.

Science.gov (United States)

Patel, Rena C; Onono, Maricianah; Gandhi, Monica; Blat, Cinthia; Hagey, Jill; Shade, Starley B; Vittinghoff, Eric; Bukusi, Elizabeth A; Newmann, Sara J; Cohen, Craig R

2015-11-01

Concerns have been raised about efavirenz reducing the effectiveness of contraceptive implants. We aimed to establish whether pregnancy rates differ between HIV-positive women who use various contraceptive methods and either efavirenz-based or nevirapine-based antiretroviral therapy (ART) regimens. We did this retrospective cohort study of HIV-positive women aged 15-45 years enrolled in 19 HIV care facilities supported by Family AIDS Care and Education Services in western Kenya between Jan 1, 2011, and Dec 31, 2013. Our primary outcome was incident pregnancy diagnosed clinically. The primary exposure was a combination of contraceptive method and efavirenz-based or nevirapine-based ART regimen. We used Poisson models, adjusting for repeated measures, and demographic, behavioural, and clinical factors, to compare pregnancy rates among women receiving different contraceptive and ART combinations. 24,560 women contributed 37,635 years of follow-up with 3337 incident pregnancies. In women using implants, adjusted pregnancy incidence was 1.1 per 100 person-years (95% CI 0.72-1.5) for nevirapine-based ART users and 3.3 per 100 person-years (1.8-4.8) for efavirenz-based ART users (adjusted incidence rate ratio [IRR] 3.0, 95% CI 1.3-4.6). In women using depot medroxyprogesterone acetate, adjusted pregnancy incidence was 4.5 per 100 person-years (95% CI 3.7-5.2) for nevirapine-based ART users and 5.4 per 100 person-years (4.0-6.8) for efavirenz-based ART users (adjusted IRR 1.2, 95% CI 0.91-1.5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, had 3.1-4.1 higher rates of pregnancy than did those using implants, with 1.6-2.8 higher rates in women using efavirenz-based ART. Although HIV-positive women using implants and efavirenz-based ART had a three-times higher risk of contraceptive failure than did those using nevirapine-based ART, these women still had lower contraceptive failure rates than did those receiving all other

The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

NARCIS (Netherlands)

Collaboration, H.-C.; Koopmans †, P.P.; Brouwer, A.M.; Dofferhoff, A.S.M.; Flier, M. van der; Groot, R. de; Hofstede, H.J.M. ter; Keuter, M.; Ven, A.J.A.M. van der; et al.,

2012-01-01

OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. DESIGN: Prospective

Evaluation of nevirapine and/or hydroxyurea with nucleoside reverse transcriptase inhibitors in treatment-naive HIV-1-infected subjects

NARCIS (Netherlands)

Blanckenberg, Daniel H.; Wood, Robin; Horban, Andrzej; Beniowski, Marek; Boron-Kaczmarska, Anna; Trocha, Hanna; Halota, Waldemar; Schmidt, Reinhold E.; Fatkenheuer, G.; Jessen, Heiko; Lange, Joep M. A.

2004-01-01

Objective: To examine the effect of adding nevirapine (NVP) and/or hydroxyurea (HU) to a triple nucleoside analogue reverse transcriptase inhibitor (NRTI) regimen in terms of efficacy and tolerability. Methods: HIV-1-infected, treatment-naive adults were randomized, using a factorial design, to add

The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

NARCIS (Netherlands)

van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

2000-01-01

OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

An unusual case of sepsis and petechial rash.

Science.gov (United States)

Gardner, Christina

2017-05-01

This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.

A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a meta-analysis

International Nuclear Information System (INIS)

Ocvirk, Janja; Heeger, Steffen; McCloud, Philip; Hofheinz, Ralf-Dieter

2013-01-01

Agents targeting the epidermal growth factor receptor (EGFR) are amongst the most extensively used of the targeted agents in the therapy of some of the most common solid tumors. Although they avoid many of the classic side effects associated with cytotoxic chemotherapy, they are associated with unpleasant cutaneous toxicities which can affect treatment compliance and impinge on patient quality of life. To date, despite a plethora of consensus recommendations, expert opinions and reviews, there is a paucity of evidence-based guidance for the management of the skin rash that occurs in the treatment of patients receiving EGFR-targeted therapies. A literature search was conducted as a first step towards investigating not only an evidence-based approach to the management of skin rash, but also with a view to designing future randomized trials. The literature search identified seven randomized trials and a meta-analysis was conducted using the data from four of these trials involving oral antibiotics. The meta-analysis of the data from these four trials suggests that prophylactic antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 42–77%. Vitamin K cream was also identified as having a potential role in the management EGFR-targeted agent induced rash. This review and meta-analysis clearly identify the need for further randomized studies of the role of oral antibiotics in this setting. The results of the ongoing randomized trials of the topical application of vitamin K cream plus or minus doxycycline and employing prophylactic versus reactive strategies are eagerly awaited

Skin rash during treatment with generic itraconazole

OpenAIRE

De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

2014-01-01

Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re...

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Oliveira Maria I

2002-01-01

Full Text Available OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19 using ELISA commercial techniques, and human herpes virus 6 (HHV 6 using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR. RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months, had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17 HPV B19 infection; 76.5% (13 in 17 HHV 6 infection; 5.9% (1 in 17 rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Maria I Oliveira

2002-04-01

Full Text Available OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19 using ELISA commercial techniques, and human herpes virus 6 (HHV 6 using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR. RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months, had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17 HPV B19 infection; 76.5% (13 in 17 HHV 6 infection; 5.9% (1 in 17 rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

Rat-bite fever presenting with rash and septic arthritis.

Science.gov (United States)

Kanechorn Na Ayuthaya, Rajyani; Niumpradit, Nucha

2005-11-01

Rat-bite fever is an uncommon disease known for its endemicity to occur worldwide. Although most patients tend to develop mild symptoms with improvement from conventional antibiotics, it can progress with severe complications with a mortality rate as high as 13% without proper treatment. The authors report a complicated case of rat bite-fever involving a 61-year old woman who presented with fever petechial rash, and septic arthritis following a rat bite. Initially, multiple antibiotics were administered but were not effective. As a consequence, invasive procedures such as arthrotomy and joint debridement were done and prolonged antibiotic was administered until clinical resolution. Since many cases do not have a history of rat bite and may present with fever, rashes, and arthritis it is essential to distinguish it from other diseases. Here, the authors will provide details on the etiology, clinical manifestations, diagnosis, and management to aid prompt detection and treatment of the disease.

The efficacy, pharmacokinetics, safety and cardiovascular risks of switching nevirapine to rilpivirine in HIV-1 patients: the RPV switch study

NARCIS (Netherlands)

Rokx, C.; Blonk, M.; Verbon, A.; Burger, D.M.; Rijnders, B.J.

2014-01-01

INTRODUCTION: Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non-nucleoside, reverse

N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance.

Directory of Open Access Journals (Sweden)

Soo-Huey Yap

2007-12-01

Full Text Available The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1 reverse transcriptase (RT consists of DNA polymerase, connection, and ribonuclease H (RNase H domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance.The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. N348I increased in prevalence from below 1% in 368 treatment-naïve individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12. N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs M41L and T215Y/F (p < 0.001, the lamivudine resistance mutations M184V/I (p < 0.001, and non-nucleoside RTI (NNRTI resistance mutations K103N and Y181C/I (p < 0.001. The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43-4.81. The appearance of N348I was associated with a significant increase in viral load (p < 0.001, which

A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

DEFF Research Database (Denmark)

Kirk, Ole; Lundgren, Jens D; Pedersen, Court

2003-01-01

BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

Mothers Knowledge and Home Management ofNappy Rash in Port ...

African Journals Online (AJOL)

TNHJOURNALPH

2006-10-10

Oct 10, 2006 ... Mothers Knowledge and Home Management ofNappy Rash in Port Harcourt, Nigeria ... of nappy-wearing babies at any given time. It is not a disease but just an ..... soap/detergent, time saving, better containment of faecal ...

Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

Science.gov (United States)

Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

2014-08-01

Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

Good performance of an immunoassay based method for nevirapine measurements in human breast milk

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Theilgaard, Zahra Persson; Chiduo, Mercy

2011-01-01

from HIV-uninfected women. Clinical samples from HIV-infected women receiving a single-dose of nevirapine were analyzed. Results: Precision and accuracy were evaluated with two concentrations of quality control materials analyzed in three replicates on four different days and was......, requires complicated extraction techniques. The ARK method employs an immunoassay technology and requires a small sample volume (40 μL) and no pre-treatment of the samples. Methods: Commercial enzyme and antibody were used and calibration standards and quality controls were prepared from pooled breast milk...

Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.

Science.gov (United States)

Kast, R E

2015-01-01

The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone's interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects. The old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses. Thus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.

A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

DEFF Research Database (Denmark)

Reekie, J; Reiss, P; Ledergerber, B

2011-01-01

The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efav...

Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report

Directory of Open Access Journals (Sweden)

Keasberry Justin

2013-01-01

Full Text Available Abstract Introduction Anti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. Case presentation We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet’s syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet’s syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently

Clinical impact of minocycline on afatinib-related rash in patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations.

Science.gov (United States)

Goto, Ayano; Ozawa, Yuichi; Koda, Keigo; Akahori, Daisuke; Koyauchi, Takashi; Amano, Yusuke; Kakutani, Takuya; Sato, Yoshiko; Hasegawa, Hirotsugu; Matsui, Takashi; Yokomura, Koshi; Suda, Takafumi

2018-03-01

The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown. We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled. Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient. A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Nappy (diaper) rash: what else besides irritant contact dermatitis?

Science.gov (United States)

Carvalho, Vânia Oliveira; Robl, Renata; Uber, Marjorie; Abagge, Kerstin Taniguchi; Marinoni, Leide Parolin; Presa, Juliana Gomes Loyola

2015-08-01

Nappy (diaper) rash is a common cutaneous disorder of infancy, and diverse dermatoses may affect this region. To perform a differential diagnosis can be challenging. We present four cases to emphasise the importance of clinical diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

MRI diagnosis of muscle denervation from herpes zoster with discordant distribution of the skin rash

Energy Technology Data Exchange (ETDEWEB)

Gupta, Amit; Sundaram, Murali [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Winalski, Carl S. [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Cleveland Clinic, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)

2014-10-15

Herpes zoster is a common disorder characterized by a painful rash along a dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle denervation injury from motor involvement is an uncommon phenomenon. Discordant distribution of the skin rash and motor nerve involvement, presenting as a skin rash in one body part and muscle weakness or pain from nerve involvement in another body part is an even more uncommonly reported finding. We present an unusual case of muscle denervation injury resulting from motor involvement of a peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous manifestations in a different dermatomal distribution. To the best of our knowledge, there has been no similar case reported in the English radiology literature. We suggest that whenever a radiologist notices MRI findings suggesting denervation injury and a cause not readily identified, VZV-related denervation injury should be included in the differential diagnosis, especially in an older immunocompromised patient. (orig.)

Prevention of mother-to-child transmission of HIV infection: Views and perceptions about swallowing nevirapine in rural Lilongwe, Malawi

Directory of Open Access Journals (Sweden)

Nyirenda Lot J

2010-06-01

Full Text Available Abstract Background In 2006 the World Health Organization described the status of prevention of mother to child transmission (PMTCT service implementation as unacceptable, with an urgent need for a renewed public health approach to improve access. For PMTCT to be effective it needs to be accessible, acceptable and affordable; however research in Africa into accessibility, uptake and acceptability of PMTCT services has been predominately urban based and usually focusing on women who deliver in hospitals. The importance of involving other community members to strengthen both PMTCT uptake and adherence, and to support women emotionally, has been advocated. Urban men's and rural traditional birth attendants' (TBAs involvement have improved uptake of HIV testing and of nevirapine. Methods A qualitative study was carried out in a rural district of Malawi's central region to explore the views about and perceptions of PMTCT antiretroviral treatment. Semi-structured interviews and focus group discussions were held with antenatal and postnatal women, fathers, grandmothers, TBAs, community leaders and PMTCT health workers. Results Two broad themes of findings emerged: those that relate to the hospital PMTCT service, and those that relate to the community. Trust in the hospital was strong, but distance, transport costs and perceived harsh, threatening health worker attitudes were barriers to access. Grandmothers were perceived to have influence on the management of labour, unlike fathers, but both were suggested as key people to ensure that babies are brought to the hospital for nevirapine syrup. TBAs were seen as powerful, local, and important community members, but some as uneducated. Conclusion PMTCT was seen as a community issue in which more than the mother alone can be involved. To support access to PMTCT, especially for rural women, there is need for further innovation and implementation research on involving TBAs in some aspects of PMTCT services

A retrospective cohort analysis comparing pregnancy rates among HIV-positive women using contraceptives and efavirenz- or nevirapine-based antiretroviral therapy in Kenya

Science.gov (United States)

PATEL, Rena C.; ONONO, Maricianah; GANDHI, Monica; BLAT, Cinthia; HAGEY, Jill; SHADE, Starley B.; VITTINGHOFF, Eric; BUKUSI, Elizabeth A.; NEWMANN, Sara J.; COHEN, Craig R.

2015-01-01

SUMMARY Background Given recent concerns of efavirenz reducing the efficacy of contraceptive implants, we sought to determine if pregnancy rates differ among HIV-positive women using various contraceptive methods and efavirenz- or nevirapine-based antiretroviral therapy (ART) regimens. Methods We conducted a retrospective cohort analysis of HIV-positive women aged 15–45 years enrolled in HIV care facilities in western Kenya from January 2011 to December 2013. Pregnancy was diagnosed clinically and the primary exposure was a combination of contraceptive method and ART regimen. We used Poisson models, adjusting for repeated measures, as well as demographic, behavioral and clinical factors, to compare pregnancy rates among women on different contraceptive/ART combinations. Findings 24,560 women contributed 37,635 years of follow-up with 3,337 incident pregnancies. Among women using implants, adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 1·1 (95% CI 0·72–1·5) and 3·3 (95% CI 1·8–4·8) per 100 women-years (w-y), respectively (adjusted incidence rate ratio (aIRR) 3·0, 95% CI 1·3–4·6). Among women using depomedroxyprogesterone acetate (DMPA), adjusted pregnancy incidence for nevirapine- and efavirenz-based ART users were 4·5 (95% CI 3·7–5·2) and 5·4 (95% CI 4·0–6·8) per 100 w-y, respectively (aIRR 1·2, 95% CI 0·91–1·5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, experienced 3·1–4·1 higher rates of pregnancy than women using implants, with 1·6–2·8 higher rates specifically among women using efavirenz-based ART. Interpretation While HIV-positive women using implants on efavirenz-based ART faced three times higher risk of contraceptive failure than those on nevirapine-based ART, these women still experienced lower contraceptive failure rates than women on all other contraceptive methods, except for intrauterine devices and permanent methods

The management of fever and petechiae: making sense of rash decisions.

Science.gov (United States)

Brogan, P A; Raffles, A

2000-12-01

In a retrospective and prospective audit of 55 children presenting to the paediatric assessment unit of a district general hospital with fever and petechial rash, 9% had significant bacterial sepsis. The "ILL criteria" (irritability, lethargy, low capillary refill) for the management of children with fever and petechiae are proposed.

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

Science.gov (United States)

Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

2016-09-01

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

Science.gov (United States)

Nishimura, Meiko; Hayashi, Mitsuhiro; Mizutani, Yu; Takenaka, Kei; Imamura, Yoshinori; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Aikawa, Hiroaki; Fujiwara, Yasuhiro; Hamada, Akinobu; Minami, Hironobu

2018-04-06

The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm 2 ; P = 0.009 in paired t -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm 3 ; P = 0.028 in paired t -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.

Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients

DEFF Research Database (Denmark)

Abdissa, A; Olsen, Mette Frahm; Yilma, D

2015-01-01

OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma...... efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS.......9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild...

Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study.

Science.gov (United States)

Van Cutsem, E; Li, C-P; Nowara, E; Aprile, G; Moore, M; Federowicz, I; Van Laethem, J-L; Hsu, C; Tham, C K; Stemmer, S M; Lipp, R; Zeaiter, A; Fittipaldo, A; Csutor, Z; Klughammer, B; Meng, X; Ciuleanu, T

2014-11-25

This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose. After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety. Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms. The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.

Hydroxyzine induced pancytopenia and petechial rashes: a rare complication

Directory of Open Access Journals (Sweden)

Ihsan Ates

2016-09-01

Full Text Available Hydroxyzine is used as an additional treatment both in symptomatic treatment of anxiety and stress caused by psychoneurosis and in organic diseases which anxiety appeared. It is used to treat pruritis caused by histamine and such allergic cases like chronic urticaria because of antihistaminic effect, atopic and contact dermatitis. In this case report, that widespread milimetric petechial rashes in all body and deep pancytopnia development is seen in a patient using hydroxyzine tablet because of pruritis at joints is disscussed. [J Contemp Med 2016; 6(3.000: 234-234

Impact of Nevirapine (NVP) Plasma Concentration on Selection of Resistant Virus in Mothers Who Received Single-Dose NVP To Prevent Perinatal Human Immunodeficiency Virus Type 1 Transmission and Persistence of Resistant Virus in Their Infected Children▿

OpenAIRE

Chaix, Marie-Laure; Ekouevi, Didier Koumavi; Peytavin, Gilles; Rouet, François; Tonwe-Gold, Besigin; Viho, Ida; Bequet, Laurence; Amani-Bosse, Clarisse; Menan, Hervé; Leroy, Valériane; Rouzioux, Christine; Dabis, François

2006-01-01

Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on ...

Two family members with a syndrome of headache and rash caused by human parvovirus B19

Directory of Open Access Journals (Sweden)

Antonio Carlos M. Pereira

Full Text Available Human parvovirus B19 infection can cause erythema infectiosum (EI and several other clinical presentations. Central nervous system (CNS involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published. Here, we describe 2 cases of B19 infection in a family presenting different clinical features. A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen. Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands. She completely recovered in 1 week. Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting. On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities. Cerebrospinal fluid analysis was normal. He completely recovered in 5 days. Acute and convalescent sera of both patients were positive for specific IgM antibody to B19. Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum. The disease may mimic meningococcemia and bacterial meningitis.

Herpes Zoster Ophthalmicus Presenting as Acute Orbital Myositis Preceding a Skin Rash: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Oh, Ha Yeun; Cho, Seong Whi [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of); Kim, Sung Hun [Dept. of Neurology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

2012-03-15

Herpes zoster ophthalmicus, in which orbital symptoms and signs appear before the onset of a skin rash, is very rare. We experienced such a case and therefore report on it via magnetic resonance imaging. A 48-year-old man with pain and swelling of left eye and headache presented 2 days before onset of a zoster skin rash. On orbit-al MRI, edematous thickening of the left lateral rectus muscle with high signal intensity was revealed. After contrast injection, the lateral rectus muscle demonstrated heterogenous enhancement. Also, diffuse contrast enhancement was noted at left preseptal space, lacrimal gland and periorbital soft tissue. The man was treated with antiviral agents and prednisolone. Two weeks later, he recovered from the skin manifestations and most of the orbital manifestations except for the diplopia and restricted lateral movement.

[Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report].

Science.gov (United States)

Marín, Jorge Alonso; Ortega, Mayra Alexandra; Sánchez, Isaura Pilar; Pacheco, José Armando

2017-06-01

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

Rash related to use of scented products. A questionnaire study in the Danish population. Is the problem increasing?

DEFF Research Database (Denmark)

Johansen, J D; Andersen, T F; Thomsen, L K

2000-01-01

. Further, it was determined whether risk of self-reported 1st-time rash from scented products had increased during the past 15 years compared to the preceding period. The sample consisted of 1537 persons, 801 female and 736 male, above the age of 15 years. The participants were interviewed person......Fragrances are used in many types of cosmetic and household products, which are an important part of everyday life in modern society. The aim of the current investigation was to describe the frequency of self-reported rash due to scented products in a random sample of the adult Danish population...

Impact of KRAS, BRAF, PIK3CA mutations, PTEN, AREG, EREG expression and skin rash in ≥ 2 line cetuximab-based therapy of colorectal cancer patients.

Directory of Open Access Journals (Sweden)

Zacharenia Saridaki

2011-01-01

Full Text Available To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC patients treated with cetuximab containing salvage chemotherapy.Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded.KRAS, BRAF and PIK3CA mutations were present in 37 (33%, 8 (7.2% and 11 (9.8% cases, respectively, PTEN was lost in 21 (19.8% cases, AREG and EREG were overexpressed in 48 (45% and 51 (49% cases. In the whole study population, time to tumor progression (TTP and overall survival (OS was significantly lower in patients with KRAS (p = 0.001 and p = 0.026, respectively or BRAF (p = 0.001 and p<0.0001, respectively mutant tumors, downregulation of AREG (p = 0.018 and p = 0.013, respectively or EREG (p = 0.002 and p = 0.004, respectively and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively. In KRAS wt patients TTP and OS was significantly lower in patients with BRAF (p = 0.0001 and p<0.0001, respectively mutant tumors, downregulation of AREG (p = 0.021 and p = 0.004, respectively or EREG (p = 0.0001 and p<0.0001, respectively and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively. TTP was significantly lower in patients with PIK3CA mutations (p = 0.01 or lost PTEN (p = 0.002. Multivariate analysis revealed KRAS (Hazard Ratio [HR] 4.3, p<0.0001, BRAF mutation (HR: 5.1, p<0.0001, EREG low expression (HR: 1.6, p = 0.021 and absence of severe/moderate skin rash (HR: 4.0, p<0.0001 as independent prognostic factors for decreased TTP. Similarly, KRAS (HR 2.9, p = 0.01, BRAF mutation (HR: 3.0, p = 0.001, EREG low expression (HR: 1.7, p = 0.021, absence of severe/moderate skin rash (HR: 3.7, p<0.0001 and the presence of undifferantited tumours (HR: 2.2, p = 0.001 were revealed as independent prognostic factors for decreased OS.These results underscore that KRAS-BRAF mutations and EREG

[Rash and fever illness caused by herpes simplex virus type 1 needs to be distinguished from hand, foot and mouth disease].

Science.gov (United States)

Zhu, Shuang-Li; Liu, Jian-Feng; Sun, Qiang; Li, Jing; Li, Xiao-Lei; Zhang, Yong; Chen, Ying; Wen, Xiao-Yun; Yan, Dong-Mei; Huang, Guo-Hong; Zhang, Bao-Min; Zhang, Bo; An, Hong-Qiu; Li, Hui; Xu, Wen-Bo

2013-06-01

An epidemic of rash and fever illnesses suspected of hand, foot and mouth disease (HFMD) occurred in Gansu Province of China in 2008, laboratory tests were performed in order to identify the pathogen that caused this epidemic. Eight clinical specimens collected from the 4 patients (each patient has throat swab and herpes fluid specimens) with rash and febrile illness, were inoculated onto RD and HEp-2 cells for virus isolation, and the viral nucleic acid was then extracted with the positive virus isolates, the dual-channel real-time reverse transcript-polymerase chain reaction (RT-PCR) was performed to detect the nucleic acid of human enterovirus (HEV) in the viral isolates at the same time. For the viral isolates with the negative results of HEV, a sequence independent single primer amplification technique (SISPA) was used for "unknown pathogen" identification. Totally, 6 viral isolates were identified as herpes simplex virus type 1 (HSV-1). Comprehensive analyses results of the clinical manifestations of the patients, epidemiological findings and laboratory test indicated that this epidemic of rash and febrile illness was caused by HSV-1. The differences among the gG region of 6 HSV-1 isolates at nucleotide level and amino acid level were all small, and the identities were up to 98. 8% and 97.9%, respectively, showing that this outbreak was caused by only one viral transmission chain of HSV-1. HSV-1 and other viruses that cause rash and febrile illnesses need differential diagnosis with HFMD. The etiology of rash and febrile illness is sometimes difficult to distinguish from the clinical symptoms and epidemiological data, the laboratory diagnosis is therefore critical.

Ibrutinib-Associated Skin Toxicity

DEFF Research Database (Denmark)

Jensen, Anders; Stausbøl-Grøn, Birgitte; Riber-Hansen, Rikke

2017-01-01

in the management of other indolent lymphomas. Just recently, based on impressive clinical trial results in heavily pretreated WM patients, a new Bruton Tyrosine Kinase-inhibitor, Ibrutinib, has been approved for the treatment of this disorder. As the use of Ibrutinib in WM outside clinical trials is still limited......, only few clinical reports illustrating treatment side effects are currently available. Here we review the current literature specific on Ibrutinib-associated rash in hematologic patients, and report on an elderly patient with WM, who developed a red maculopapular non-pruritic rash 12 weeks after...... starting Ibrutinib therapy. Without modifications of the ongoing Ibrutinib schedule, the rash regressed within two weeks of treatment with topical steroid-containing dermatological compounds....

Association of Allelic Interaction of Single Nucleotide Polymorphisms of Influx and Efflux Transporters Genes With Nonhematologic Adverse Events of Docetaxel in Breast Cancer Patients.

Science.gov (United States)

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-05-04

Nonhematologic adverse events (AEs) of docetaxel constitute an extra burden in the treatment of cancer patients and necessitate either a dose reduction or an outright switch of docetaxel for other regimens. These AEs are frequently associated with genetic polymorphisms of genes encoding for proteins involved docetaxel disposition. Therefore, we investigated that association in Malaysian breast cancer patients. A total of 110 Malaysian breast cancer patients were enrolled in the present study, and their blood samples were investigated for different single nucleotide polymorphisms using polymerase chain reaction restriction fragment length polymorphism. AEs were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. Fatigue, nausea, oral mucositis, and vomiting were the most common nonhematologic AEs. Rash was associated with heterozygous and mutant genotypes of ABCB1 3435C>T (P A/T reported more fatigue than those carrying the heterozygous genotype GA (P T polymorphism could be a potential predictive biomarker of docetaxel-induced rash, and homozygous wild-type ABCB1 2677G>A/T might predict for a greater risk of fatigue. In addition, the concurrent presence of specific alleles could be predictive of vomiting, nausea, and oral mucositis. Copyright © 2018 Elsevier Inc. All rights reserved.

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

Science.gov (United States)

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-03-01

Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

A 30-Year-Old Man with HIV, Fever, and a Rash

Directory of Open Access Journals (Sweden)

Radhika Shah

2018-03-01

Full Text Available Patients who present with papular rashes have a wide differential diagnosis particularly in the setting of immune compromise. A 30-year-old male diagnosed with HIV since 2009, never on antiretroviral therapy, with a nadir CD4 count of 333 cells/mm3 and a current viral load of 44,300 copies/mL, presented with a diffuse monomorphic papular eruption that began on his trunk and extremities and subsequently spread to the penis and scrotum, sparing the distal acral sites. A thorough infectious workup revealed a positive rapid plasma reagin (RPR and varicella IgM and IgG antibodies. Interestingly, the patient had been diagnosed and treated for syphilis in the past with a recent downtrending RPR drawn prior to hospitalization. Repeat RPR was elevated and a preliminary histopathology report demonstrated folliculocentric inflammation with lymphocytes, plasma cells, and polymorphonuclear leukocyte predominance supported the diagnosis of syphilis. After receiving intramuscular penicillin G benzathine, he developed intermittent fevers and new papules. Intravenous (IV acyclovir was initiated for presumed disseminated varicella given his positive varicella-zoster virus IgM and IgG. However, final pathology results revealed a large spirochete burden. The fevers and rash progression were attributed to the development of a Jarisch-Herxheimer reaction. IV acyclovir was discontinued and he completed a course of intramuscular penicillin G benzathine. He was also given a course of doxycycline for rectal chlamydia which was diagnosed during hospitalization.

In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats.

Science.gov (United States)

Usach, Iris; Ferrer, José-Maria; Peris, José-Esteban

2018-04-17

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (K i  = 4.01, 3.97 and 4.40 μM, respectively). Time-dependent inhibition of the NVP metabolism was also detected, with a 2.5-fold reduction in the IC 50 values of NT for 2-, 3-, and 12-OH-NVP formation when NT was preincubated with the microsomal suspension in the presence of an NADPH-generating system. A concentration-dependent inhibition of the formation of NVP metabolites by the main NT metabolite (10-OH-NT) was also observed, however, the inhibitory potency of 10-OH-NT was much lower than that of the parent drug. The apparent hepatic intrinsic clearance of NVP determined in these in vitro experiments was used to predict the in vivo clearance of NVP using the "well-stirred" and the "parallel-tube" models, resulting in values close to those previously observed in vivo clearance. Finally, a good prediction of the increase in the plasma concentrations of NVP when co-administered with NT was obtained employing the inhibitory constant of NT determined in vitro and the estimated plasma concentration of NT entering the liver. Copyright © 2018. Published by Elsevier Inc.

Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

Science.gov (United States)

Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun Ju; Son, Hwa-Young; Moon, Kyoung-Sik

2017-01-01

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

Prognostic implications of active discoid lupus erythematosus and malar rash at the time of diagnosis of systemic lupus erythematosus: Results from a prospective cohort study.

Science.gov (United States)

Drucker, A M; Su, J; Mussani, F; Siddha, S K; Gladman, D D; Urowitz, M B

2016-04-01

Cutaneous lupus erythematosus (CLE) may have prognostic implications for systemic lupus erythematosus (SLE). We aimed to determine the impact of discoid lupus erythematosus (DLE) and malar rash on SLE disease activity. Data were analyzed from the Toronto Lupus Clinic prospective cohort study. We compared SLE patients with active DLE or malar rash at SLE diagnosis to SLE patients who never developed CLE. Outcomes were assessed at one and five years, including Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (AMS). A total of 524 SLE patients (284 without CLE, 65 with DLE, and 175 with malar rash) were included. Mean AMS scores in patients without CLE at one and five years were 5.96 ± 5.06 and 4.00 ± 3.52, which did not differ significantly from scores at one (6.93 ± 5.31, p = 0.17) and five years (4.29 ± 2.62, p = 0.63) in the DLE group. In patients with malar rash, AMS scores at one (8.30 ± 6.80, p < 0.001) and five years (5.23 ± 3.06, p = 0.004) were higher than controls without CLE. Malar rash may be a marker of more severe systemic disease over time, while DLE has no significant impact on general SLE disease activity. © The Author(s) 2015.

An epidemiological investigation into an outbreak of rash illness among methadone maintenance clients in Australia.

Science.gov (United States)

McAnulty, Jeremy M; Jauncey, Marianne E; Monger, Claire K; Hailstone, Susan T; Alam, Noore K M; Mannes, Trish F; Capon, Adam G; Irvine, Katie; Armstrong, Paul K; Kaldor, John M

2007-05-01

In late 2004, NSW Health received several reports of a serious desquamating rash among clients of the methadone program. We sought to identify the extent and likely cause of this outbreak. We initiated active surveillance for cases throughout Australia, a survey of dosing points in NSW, and a case control study of clients receiving methadone syrup (MS) at two clinics. Between October 2004 and March 2005, 388 cases were identified, largely in NSW. The dosing point survey found almost all cases were clients prescribed MS (attack rate 4.5%). In multivariate analysis of data from dosing points that dispensed MS, use of take away doses or location of the dosing point in greater western Sydney were associated with illness. In the case control study, MS injection, use of street MS, high doses of MS, frequent takeaway doses, or use of benzodiazepines were associated with illness. Testing found no abnormality in associated batches of MS. Batches of MS temporally associated with the outbreak were quarantined from use and the outbreak subsided. While a direct causal link could not be established, available evidence suggests that a contaminant may have caused the outbreak. Epidemiological analyses are important for assessing concerns about product safety following marketing approval.

Seizure freedom after lamotrigine rash: a peculiar phenomenon in epilepsy.

Science.gov (United States)

Kakisaka, Yosuke; Jin, Kazutaka; Kato, Kazuhiro; Iwasaki, Masaki; Nakasato, Nobukazu

2014-01-01

A 57-year-old right-handed woman with a history of left frontal lobe stroke had experienced episodes of language-expression difficulty followed by paraphasia lasting for approximately 30 seconds two years earlier. She was diagnosed with left frontal lobe epilepsy, and a lamotrigine regimen was initiated. This treatment had to be stopped five weeks after initiation because she developed a rash, and her drug lymphocyte stimulation test result was positive. Interestingly, she has since remained seizure free without requiring any antiepileptic medications. This adult case with a peculiar clinical course provides support for the hypothesis of immunomodulation process involvement in epilepsy, a phenomenon that was previously mainly seen in pediatric patients.

Antipsychotic-associated psoriatic rash - a case report

DEFF Research Database (Denmark)

Bujor, Camelia-Eugenia; Vang, Torkel; Nielsen, Jimmi

2017-01-01

BACKGROUND: Antipsychotics are a heterogeneous group of drugs. Although, antipsychotics have been used for years, unexpected side effects may still occur. With this case report we focus on a possible association between psoriasis and antipsychotics. Data on the patient's course of psychiatric...... disease, onset of psoriasis and its evolution were extracted from the patient's medical files. CASE PRESENTATION: We present a case of a 21-year-old female diagnosed with schizophrenia. She was initially treated with quetiapine, and later switched to aripiprazole due to weight gain. After initiation...

Not all that rashes is measles:

International Nuclear Information System (INIS)

Ibrahim, S. A.; Mustafa, O. A.

1998-01-01

Measles is a major cause of infant mortality in third world countries, leading to approximately one million deaths each year. The WHO aims to globally eradicate measles virus at the beginning of the next century, which will need a major effort in particular in countries like Sudan. To achieve goal epidemiological studies I am needed to estimate the magnitude of the problem for which accurate diagnostic test are needed. We therefore conducted a study in El hag Yousif area (population 500 000) in Khartoum North where measles is prevalent despite vaccination effort by EPI. We studied the accuracy of the WHO criteria for clinical diagnosis in comparison with laboratory diagnosis during a one-year period. A total of 145 under five suspected measles cases were identified by active, case finding and examined. 111 cases fully complied with the WHO criteria for diagnosis of clinical measles. Out of 103 clinical measles cases, tested using prototype rapid measles test IgM Elisa and Pcr, 77(75%) were measles positive. A battery of virus test was run on 21 sera out of the 26(25%) measles negatives: Herpes virus-6, Epstein-Bar and Dengue viruses were detected in five, one and one case, respectively. It was concluded that one out of every four cases diagnosed by the clinical as measles rash is probably caused by other viruses. (Author)

Another Look at Impulsivity: A Meta- Analytic Review Comparing Specific Dispositions to Rash Action in their Relationship to Bulimic Symptoms

Science.gov (United States)

Fischer, Sarah; Smith, Gregory T.; Cyders, Melissa A.

2008-01-01

Recent advances in personality theory indicate that there are distinct constructs that dispose individuals to rash action and risky behavior, as opposed to one broad trait of impulsivity. Two are emotion based, two represent deficits in conscientiousness, and one is sensation seeking. Previous studies of impulsivity and its relationship to bulimia nervosa have yielded mixed findings. The authors applied this advance in personality theory to the study of bulimia nervosa (BN) to test the hypothesis that the emotion-based disposition of negative urgency (the tendency to act rashly when distressed) relates most strongly to BN symptoms. A meta analysis of 50 articles indicated the following. Negative urgency had by far the largest effect size (weighted r = .38), followed by sensation seeking (weighted r = .16); lack of planning (weighted r = .16) and lack of persistence (weighted r = .08). Methodological moderators of the effect of distinct traits on BN symptoms were the use of scales that precisely measured one construct as opposed to general impulsivity scales that measured several constructs, clinical vs. non-clinical samples, and whether or not the personality scale was translated from its original language or not. Negative urgency appears especially important for BN; more broadly, researchers should consider the role of emotion-based dispositions to rash acts in their risk theories. PMID:18848741

HIV and pregnancy: Maternal and neonatal evolution HIV y embarazo: Evolución materna y neonatal

Directory of Open Access Journals (Sweden)

Diego Cecchini

2011-10-01

Full Text Available Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006. Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median: 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55% or a protease inhibitor (32%]. Overall incidence of toxicity was 12.5%: rash (8%, anemia (3.5% and hepatotoxicity (1%. Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads La información sobre aspectos epidemiológicos, seguridad de drogas antirretrovirales y evolución de mujeres embarazadas HIV positivas y sus hijos es limitada en la Argentina. Realizamos un análisis retrospectivo de registros de embarazadas HIV positivas asistidas en Helios Salud, Buenos Aires, Argentina (1997-2006. Las variables asociadas con parto prematuro y complicaciones neonatales se estudiaron mediante análisis univariado y regresión logística. Estudiamos 204 binomios madre-hijo. Edad materna (mediana: 29 años, 32.5% sin diagnóstico previo de HIV. Recuento de linfocitos T CD4+ (mediana: 417 células/μl. El 98% recibió tratamiento antirretroviral durante el embarazo [dos análogos de nucleósidos más nevirapina (55% o un inhibidor de proteasa (32%]. La incidencia global de toxicidad fue 12.5%: erupción cutánea (8%, anemia (3.5% y hepatotoxicidad (1%. La exposición a nevirapina se asoció con rash. El 81% y 50% alcanzaron cargas virales <1000 y <50 copias/ml preparto, respectivamente. Cesárea programada: 68

MEDICAL PRACTICE IN CHILDREN PRESENTING FEVER WITH PETECHIAL RASH TO AN EMERGENCY DEPARTMENT.

Science.gov (United States)

Dumitrascu-Biris, Ioana; Chirita-Emandi, Adela; Lambert, Imelda; Marginean, Otilia; Sharif, Farhana

2016-01-01

The association of fever and petechiae in children is one of the most alarming findings for a paediatrician. To quickly distinguish between benign and life-threatening conditions is challenging in many cases. We aimed to evaluate the clinical practice of children presenting with fever and petechiae as initial symptoms. 41 patients (age 3 months-11 years) presenting with fever and petechiae were identified in an Emergency Paediatric Assessment Unit over a period of 9 months. General data, symptoms and signs were assessed for each patient. The work-up consisted in: complete blood count, inflammatory tests, coagulation tests, Monospot test, nasopharyngeal rapid tests, blood culture, and cerebrospinal fluid culture where appropriate. Most children were 6 mg/l was poorly correlated with serious illness. The following variables were strongly associated with serious illness: ill appearance, shivering, lethargy, back rigidity, ESR>50 mm/h and prolonged capillary refill time. 59% (24/41) of children were treated with antibiotics, however, at discharge 42%(10/24) of them, did not have a work-up suggestive for a bacterial illness. Screening for low prevalence but high morbidity conditions, as the meningococcal disease, with an extensive work-up is time and resource consuming and may lead to unmotivated antibiotic use. Larger studies are needed to change the emergency practice for management of fever and rash.

A 25-Year-Old Male with Orogenital Ulcers, Rash, and Difficulty Swallowing

Directory of Open Access Journals (Sweden)

Lauren N. Ko

2017-11-01

Full Text Available A 25-year-old otherwise healthy male presented with new-onset odynophagia, rash, and orogenital ulcers. Despite treatment with antibiotics for presumed bacterial pharyngitis, the patient remained symptomatic, with abnormal vital signs and laboratory values. Upon dermatology consultation and histopathologic correlation, he was diagnosed with Behçet disease. Behçet disease is a rare rheumatologic condition that presents with recurrent oral ulcers and varying degrees of ophthalmic, neurologic, cardiac, and vascular disease. Given its protean nature, the treatment of Behçet disease is tailored to the patient's presentation and severity of organ involvement. Following treatment with colchicine and prednisone, the patient's symptoms improved rapidly.

Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine.

Science.gov (United States)

Chintalapudi, Ramprasad; Murthy, T E G K; Lakshmi, K Rajya; Manohar, G Ganesh

2015-01-01

The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 2(2) factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 2(2) factorial designs. The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology.

The intra-oceanic Cretaceous (~ 108 Ma) Kata-Rash arc fragment in the Kurdistan segment of Iraqi Zagros suture zone: Implications for Neotethys evolution and closure

Science.gov (United States)

Ali, Sarmad A.; Ismail, Sabah A.; Nutman, Allen P.; Bennett, Vickie C.; Jones, Brian G.; Buckman, Solomon

2016-09-01

The Kata-Rash arc fragment is an allochthonous thrust-bound body situated near Penjween, 100 km northeast of Sulymannia city, Kurdistan Region, within the Iraqi portion of the Zagros suture zone. It forms part of the suprasubduction zone 'Upper Allochthon' terranes (designated as the Gimo-Qandil Group), which is dominated by calc-alkaline andesite and basaltic-andesite, rhyodacite to rhyolite, crosscut by granitic, granodioritic, and dioritic dykes. Previously, rocks of the Kata-Rash arc fragment were interpreted as a part of the Eocene Walash volcanic group. However, SHRIMP zircon U-Pb dates on them of 108.1 ± 2.9 Ma (Harbar volcanic rocks) and 107.7 ± 1.9 Ma (Aulan intrusion) indicate an Albian-Cenomanian age, which is interpreted as the time of igneous crystallisation. The Aulan intrusion zircons have initial εHf values of + 8.6 ± 0.2. On a Nb/Yb-Th/Yb diagram, all Kata-Rash samples fall within the compositional field of arc-related rocks, i.e. above the mid-ocean-ridge basalt (MORB)-ocean island basalt (OIB) mantle array. Primitive-mantle-normalised trace-element patterns for the Kata-Rash samples show enrichment in the large ion lithophile elements and depletion in the high-field-strength elements supporting their subduction-related character. Low Ba/La coupled with low La/Yb and Hf/Hf* 3000 km continuity of Cretaceous arc activity (Oman to Cyprus), that consumed Neotethyian oceanic crust between Eurasia and the Gondwanan fragment Arabia.

Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy

Directory of Open Access Journals (Sweden)

B Akshaya Srikanth

2012-01-01

Full Text Available To estimate the incidence of adverse drug reactions (ADRs in Human immune deficiency virus (HIV patients on highly active antiretroviral therapy (HAART. To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%. The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52% was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm 3 with comorbid conditions.

Impact of glutathione transferases genes polymorphisms in nevirapine adverse reactions: a possible role for GSTM1 in SJS/TEN susceptibility.

Science.gov (United States)

Ciccacci, Cinzia; Latini, Andrea; Politi, Cristina; Mancinelli, Sandro; Marazzi, Maria C; Novelli, Giuseppe; Palombi, Leonardo; Borgiani, Paola

2017-10-01

Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions. We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP. A case/control association study was performed. We also counted the number of risk alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes. Among patients, 27 had developed SJS/TEN and 76 had developed hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This association is also observed when other risk factors are taken into account, by a multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting analysis revealed a significantly higher risk for SJS/TEN in patients carrying three or four risk alleles. Moreover, all subjects with five or six risk alleles developed SJS/TEN, while subjects without any risk alleles were present only in the control group. We observed an association between GSTM1 and SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a genetic risk profile for SJS/TEN susceptibility.

Hepatocyte spheroids as a competent in vitro system for drug biotransformation studies: nevirapine as a bioactivation case study.

Science.gov (United States)

Pinheiro, Pedro F; Pereira, Sofia A; Harjivan, Shrika G; Martins, Inês L; Marinho, Aline T; Cipriano, Madalena; Jacob, Cristina C; Oliveira, Nuno G; Castro, Matilde F; Marques, M Matilde; Antunes, Alexandra M M; Miranda, Joana P

2017-03-01

The development of metabolically competent in vitro models is of utmost importance for predicting adverse drug reactions, thereby preventing attrition-related economical and clinical burdens. Using the antiretroviral drug nevirapine (NVP) as a model, this work aimed to validate rat hepatocyte 3D spheroid cultures as competent in vitro systems to assess drug metabolism and bioactivation. Hepatocyte spheroids were cultured for 12 days in a stirred tank system (3D cultures) and exposed to equimolar dosages of NVP and its two major Phase I metabolites, 12-OH-NVP and 2-OH-NVP. Phase I NVP metabolites were detected in the 3D cultures during the whole culture time in the same relative proportions reported in in vivo studies. Moreover, the modulation of SULT1A1 activity by NVP and 2-OH-NVP was observed for the first time, pointing their synergistic effect as a key factor in the formation of the toxic metabolite (12-sulfoxy-NVP). Covalent adducts formed by reactive NVP metabolites with N-acetyl-L-cysteine and bovine serum albumin were also detected by high-resolution mass spectrometry, providing new evidence on the relative role of the reactive NVP metabolites, 12-sulfoxy-NVP, and NVP quinone methide, in toxicity versus excretion pathways. In conclusion, these results demonstrate the validity of the 3D culture system to evaluate drug bioactivation, enabling the identification of potential biomarkers of bioactivation/toxicity, and providing new evidence to the mechanisms underlying NVP-induced toxic events. This model, integrated with the analytical strategies described herein, is of anticipated usefulness to the pharmaceutical industry, as an upstream methodology for flagging drug safety alerts in early stages of drug development.

Towards Predictive Association Theories

DEFF Research Database (Denmark)

Kontogeorgis, Georgios; Tsivintzelis, Ioannis; Michelsen, Michael Locht

2011-01-01

Association equations of state like SAFT, CPA and NRHB have been previously applied to many complex mixtures. In this work we focus on two of these models, the CPA and the NRHB equations of state and the emphasis is on the analysis of their predictive capabilities for a wide range of applications....... We use the term predictive in two situations: (i) with no use of binary interaction parameters, and (ii) multicomponent calculations using binary interaction parameters based solely on binary data. It is shown that the CPA equation of state can satisfactorily predict CO2–water–glycols–alkanes VLE...

Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique.

Directory of Open Access Journals (Sweden)

Francisco Antunes

Full Text Available Single-dose nevirapine (sd-NVP has been the main option for prevention of mother-to-child transmission (PMTCT of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM in the context of PMTCT.To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012 at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq. Sequencing was performed with ABI 3100 (Applied Biosystems. Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12 months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs for PMTCT. ARV RAM were detected in 43 (54.4% of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16 and Y181C (n = 15. NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34 and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32. In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66.We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.

Randomized double-blind trial of prophylactic topical Evozac® Calming Skin Spray for gefitinib-associated acne-like eruption

Directory of Open Access Journals (Sweden)

Wang Y

2014-07-01

Full Text Available Yalan Wang,* Yunpeng Yang,* Jinxia Xu, Juan Yu, Xia Liu, Ruizhen Gao, Li Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China *These authors contributed equally to this work Background: "Gefitinib" is a first-generation epidermal growth factor receptor tyrosine-kinase inhibitor. More than half of patients receiving gefitinib develop acne-like eruption. Evozac® Calming Skin Spray (Evaux Laboratoires, Évaux-les-Bains, France is made of Évaux thermal spring water and commonly used for the treatment of dermatological toxicities caused by anti- epidermal growth factor receptor therapy. The aim of the study reported here was to test the effect of Evozac Calming Skin Spray on the prevention of rash in patients receiving gefitinib. Methods: Non-small-cell lung cancer patients preparing to initiate gefitinib therapy were randomly assigned to apply Evozac Calming Skin Spray or physiological saline to the face three times a day. The treatment was started on the same day as initiation of gefitinib therapy and continued for 4 weeks. Results: A total of 51 patients in the Evozac Calming Skin Spray group and 50 patients in the physiological saline group completed the study per the protocol. The number of facial lesions peaked at the end of 3 weeks in both groups. There were significantly fewer lesions in the Evozac Calming Skin Spray group than in the physiological saline group at the end of 1 week (0.25 versus [vs] 1.10, P=0.031 and 3 weeks (6.67 vs 12.26, P=0.022. Patients from the Evozac Calming Skin Spray group also developed fewer facial lesions at the end of 2 weeks and 4 weeks, however, the difference was not statistically significant. At the end of 4 weeks, fewer patients from the Evozac Calming Skin Spray group developed rash of grade 2 or greater severity (17.6% vs 36.0%, P=0.037, or experienced rash-associated

Severe cutaneous reaction to cetuximab with possible association with the use of over-the-counter skin care products in a patient with oropharyngeal cancer.

Science.gov (United States)

Waris, Waris; Naik, Seeta; Idrees, Imran; Taha, Hesham; Camosino, Linda; Mehrishi, Anshu; Saif, Muhammad Wasif

2009-01-01

The management of locally advanced head and neck cancer remains a challenge to most oncologists and their patients. Treatment with epithelial growth factor receptor inhibitors (EGFRIs) is associated with a good response. Cetuximab, a chimeric monoclonal antibody directed against epithelial growth factor receptor (EGFR), in combination with radiation therapy is indicated for the treatment of locally advanced squamous cell carcinoma of the head and neck. Although a mild acneiform skin rash (Grade 1, 2) is very common in these patients, severe rash (Grade 3) is uncommon. A 61-year-old African American man with locally advanced oropharyngeal cancer was treated with cetuximab and radiation. He developed a sudden flare-up of a skin rash after the 5th cycle of cetuximab following use of over-the-counter (OTC) skin care remedies. The rash manifested with severe maculopapular eruption and erythematous rash, along with desquamation and exfoliation of the skin, mainly on the face and neck area. The patient denied any extraordinary sun exposure. Cetuximab and radiation therapy were held for 1 week and the rash was treated with doxycycline, diphenhydramine, and continued use of natural emollient (Vaseline petroleum jelly). After 1 week, a dramatic improvement of the facial rash was noticed. Our report describes a sudden flare-up of a skin rash (Grade 3) after the 5th cycle of cetuximab following use of OTC skin care remedies, which was unusual for this patient, suggesting a possible relation to the therapy. Skin crucially depends on EGFR for its normal function and becomes extremely sensitive during cetuximab therapy. Topical OTC acne and dry skin remedies can suddenly change the mild acneiform rash into severe skin toxicity associated with marked desquamation and exfoliation. Avoidance of further skin damage caused by topical applications and the use of doxycycline and diphenhydramine show a significant success in the management of skin toxicity.

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

Directory of Open Access Journals (Sweden)

Phairote Teeranaipong

Full Text Available Etravirine(ETR can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV. However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV- and nevirapine(NVP-based regimens.Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01. K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01. The results from all three scoring systems were concordant. 165(11.1% and 161(10.9% patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85. 195 (32.2% and 191 (31.6% patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79. The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01.The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

Science.gov (United States)

Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ohata, Pirapon June; Avihingsanon, Anchalee; Ruxrungtham, Kiat; Putcharoen, Opass

2016-01-01

Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

Science.gov (United States)

Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

2014-01-01

The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

Available studies fail to provide strong evidence of increased risk of diarrhea mortality due to measles in the period 4-26 weeks after measles rash onset.

Science.gov (United States)

Jackson, Bianca D; Black, Robert E

2017-11-07

suggests that the risk of measles-associated diarrhea mortality is largely limited to the 5-week period 1 week prior to and 4 weeks after measles rash onset, and that there is no increased risk of diarrhea mortality in the longer-term caused by measles.

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: a systematic review and meta-analysis.

Science.gov (United States)

Bera, Ebrahim; Mia, Rafiq

2012-10-08

The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

Science.gov (United States)

Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2014-01-01

Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (Pmalnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

[Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

Science.gov (United States)

Gao, Shi-cheng; Gui, Xi-en; Deng, Li-ping; Zhang, Yong-xi; Yan, Ya-jun; Rong, Yu-ping; Liang, Ke; Yang, Rong-rong

2010-09-01

To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

GAPIT: genome association and prediction integrated tool.

Science.gov (United States)

Lipka, Alexander E; Tian, Feng; Wang, Qishan; Peiffer, Jason; Li, Meng; Bradbury, Peter J; Gore, Michael A; Buckler, Edward S; Zhang, Zhiwu

2012-09-15

Software programs that conduct genome-wide association studies and genomic prediction and selection need to use methodologies that maximize statistical power, provide high prediction accuracy and run in a computationally efficient manner. We developed an R package called Genome Association and Prediction Integrated Tool (GAPIT) that implements advanced statistical methods including the compressed mixed linear model (CMLM) and CMLM-based genomic prediction and selection. The GAPIT package can handle large datasets in excess of 10 000 individuals and 1 million single-nucleotide polymorphisms with minimal computational time, while providing user-friendly access and concise tables and graphs to interpret results. http://www.maizegenetics.net/GAPIT. zhiwu.zhang@cornell.edu Supplementary data are available at Bioinformatics online.

Smart Rash Driver System via Internet of Things (IoT

Directory of Open Access Journals (Sweden)

Sheau Tong Kong

2017-01-01

Full Text Available Nearly half a million accidents on Malaysians road occur in 2015. The aim of this research is to detect car speed, capture the photo of the speeding car and then transfer the data like car speed, date and time, location and lane number to an online database. A distance sensor is used to measure the distance range between two points on the road. The ESP8266 NodeMCU will be the control unit to process the data and calculate the speed with the formula of speed equal to distance over time. The ESP8266 NodeMCU is also a Wi-Fi module to help in transferring data via IoT to an online database. The Google spreadsheet acted as an online database and will receive all the data if detected a speeding car. In conclusion, the Smart Rash Driver System is successfully invented and able to detect vehicle speed, capture the photo of over speed vehicle and save it to the SD card and lastly transfer all data via IoT to the Google Spreadsheet. This invention will be able to help to decrease the road accident rate efficiently.

Neutralization of IL-8 prevents the induction of dermatologic adverse events associated with the inhibition of epidermal growth factor receptor

DEFF Research Database (Denmark)

Bangsgaard, Nannie; Houtkamp, Mischa; Schuurhuis, Danita H

2012-01-01

Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance to treatm......Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance......, characterized by acute follicular neutrophil-rich hair follicle inflammation, and thus mimicked adverse events induced by systemic administration of EGFR inhibitors. In this model, we tested the hypothesis that neutrophils, attracted by IL-8, play a central role in the observed rash. Indeed, concomitant local...

Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash.

Science.gov (United States)

Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole; Overgaard, Jens; Pfeiffer, Per

2017-07-01

Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash. Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m 2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR. Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area. The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.

Predicting genotypes environmental range from genome-environment associations.

Science.gov (United States)

Manel, Stéphanie; Andrello, Marco; Henry, Karine; Verdelet, Daphné; Darracq, Aude; Guerin, Pierre-Edouard; Desprez, Bruno; Devaux, Pierre

2018-05-17

Genome-environment association methods aim to detect genetic markers associated with environmental variables. The detected associations are usually analysed separately to identify the genomic regions involved in local adaptation. However, a recent study suggests that single-locus associations can be combined and used in a predictive way to estimate environmental variables for new individuals on the basis of their genotypes. Here, we introduce an original approach to predict the environmental range (values and upper and lower limits) of species genotypes from the genetic markers significantly associated with those environmental variables in an independent set of individuals. We illustrate this approach to predict aridity in a database constituted of 950 individuals of wild beets and 299 individuals of cultivated beets genotyped at 14,409 random Single Nucleotide Polymorphisms (SNPs). We detected 66 alleles associated with aridity and used them to calculate the fraction (I) of aridity-associated alleles in each individual. The fraction I correctly predicted the values of aridity in an independent validation set of wild individuals and was then used to predict aridity in the 299 cultivated individuals. Wild individuals had higher median values and a wider range of values of aridity than the cultivated individuals, suggesting that wild individuals have higher ability to resist to stress-aridity conditions and could be used to improve the resistance of cultivated varieties to aridity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Indian Adolescent Living with HIV-AIDS: Current Clinical Scenario.

Science.gov (United States)

Joshi, Kavita S; Bhaware, Bhushan D; Pazare, Amar R

2017-07-01

Statistics suggest that, HIV has now largely become the disease of young patients. Hence, the adolescent HIV/AIDS needs to be handled and managed separately from adult HIV. Relatively fewer Indian data exist to characterize the associations in adolescents and young adults infected with HIV disease. The present study explores the current challenges in the management of HIV infected adolescents. The study was aimed at evaluating, relationship between CD4 count and duration of antiretroviral therapy (ART), effects of ART on body mass index and the adverse effects of antiretroviral drugs in adolescent HIV positive patients. This was a cross-sectional study involving 60 HIV positive adolescent patients attending tertiary care Institute KEM Hospital, Parel over duration of one year conducted at Mumbai. Patients on ART between age group 12 to 19 years. ART naïve patients were excluded from the study. 60 adolescent HIV positive patients attended our OPD including 37 males (61.67%) and 23 females (38.33%).The most common mode of transmission was vertical (80%). Education level was: school dropouts - 15%, primary education - 30%, Completed SSC - 31.7%, higher secondary - 23%. Among ADRs were 12 (63.15%) cases of anaemia due to Zidovudine, 4 (21.05%) hepatitis due to Nevirapine, 2 (10.52%) Tenofovir induced AKI and 1 (5.26%) Nevirapine rash. Wilcoxon matched pairs test showed a highly significant increase in the BMI (p ART under government programme has increased the duration of survival of the adolescent population with HIV. Treatment with HAART showed a favourable response with a statistical significant increase in CD4 count. Longer the duration of HAART, higher was the gain in CD4 count. Indian adolescent receiving long term ART, Lipodystrophy is not a troubling issue. Indian adolescent seems to be more tolerance of ART than the other parts of world.

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

Science.gov (United States)

Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-03-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

Rash with DERMABOND PRINEO Skin Closure System Use in Bilateral Reduction Mammoplasty: A Case Series.

Science.gov (United States)

Knackstedt, R W; Dixon, J A; O'Neill, P J; Herrera, F A

2015-01-01

Background. Bilateral reduction mammoplasty is a common plastic surgery procedure that can be complicated by unfavorable scar formation along incision sites. Surgical adhesives can be utilized as an alternative or as an adjunct to conventional suture closures to help achieve good wound tension and provide an adequate barrier with excellent cosmesis. The recently introduced DERMABOND PRINEO Skin Closure System Skin Closure System combines the skin adhesive 2-octyl cyanoacrylate with a self-adhering polyester-based mesh. Proposed benefits of wound closure with DERMABOND PRINEO Skin Closure System, used with or without sutures, include its watertight seal, easy removal, microbial barrier, even distribution of tension, and reduction in wound closure time. Although allergic reactions to 2-octyl cyanoacrylate have been reported, few allergic reactions to DERMABOND PRINEO Skin Closure System have been noted in the literature. This case series describes three patients who experienced an allergic reaction to DERMABOND PRINEO Skin Closure System after undergoing elective bilateral reduction mammoplasties at our institution to further explore this topic. Methods. Retrospective chart review of bilateral reduction mammoplasty patients who received DERMABOND PRINEO Skin Closure System dressing at our institution was performed. Results. Three patients were identified as having a rash in reaction to DERMABOND PRINEO Skin Closure System after bilateral reduction mammoplasty. All three patients required systemic steroid treatment to resolve the rash. One patient was identified as having a prior adhesive reaction. Conclusions. DERMABOND PRINEO Skin Closure System has demonstrated its efficacy in optimizing scar healing and appearance. However, as we demonstrate these three allergic reactions to DERMABOND PRINEO Skin Closure System, caution must be utilized in its usage, namely, in patients with a prior adhesive allergy and in sites where moisture or friction may be apparent.

Rash with DERMABOND PRINEO Skin Closure System Use in Bilateral Reduction Mammoplasty: A Case Series

Directory of Open Access Journals (Sweden)

R. W. Knackstedt

2015-01-01

Full Text Available Background. Bilateral reduction mammoplasty is a common plastic surgery procedure that can be complicated by unfavorable scar formation along incision sites. Surgical adhesives can be utilized as an alternative or as an adjunct to conventional suture closures to help achieve good wound tension and provide an adequate barrier with excellent cosmesis. The recently introduced DERMABOND PRINEO Skin Closure System Skin Closure System combines the skin adhesive 2-octyl cyanoacrylate with a self-adhering polyester-based mesh. Proposed benefits of wound closure with DERMABOND PRINEO Skin Closure System, used with or without sutures, include its watertight seal, easy removal, microbial barrier, even distribution of tension, and reduction in wound closure time. Although allergic reactions to 2-octyl cyanoacrylate have been reported, few allergic reactions to DERMABOND PRINEO Skin Closure System have been noted in the literature. This case series describes three patients who experienced an allergic reaction to DERMABOND PRINEO Skin Closure System after undergoing elective bilateral reduction mammoplasties at our institution to further explore this topic. Methods. Retrospective chart review of bilateral reduction mammoplasty patients who received DERMABOND PRINEO Skin Closure System dressing at our institution was performed. Results. Three patients were identified as having a rash in reaction to DERMABOND PRINEO Skin Closure System after bilateral reduction mammoplasty. All three patients required systemic steroid treatment to resolve the rash. One patient was identified as having a prior adhesive reaction. Conclusions. DERMABOND PRINEO Skin Closure System has demonstrated its efficacy in optimizing scar healing and appearance. However, as we demonstrate these three allergic reactions to DERMABOND PRINEO Skin Closure System, caution must be utilized in its usage, namely, in patients with a prior adhesive allergy and in sites where moisture or friction may

Congenital Cutaneous Candidiasis: Prompt Systemic Treatment Is Associated With Improved Outcomes in Neonates.

Science.gov (United States)

Kaufman, David A; Coggins, Sarah A; Zanelli, Santina A; Weitkamp, Jörn-Hendrik

2017-05-15

Congenital cutaneous candidiasis (CCC) is a challenging diagnosis due to various rash presentations. Inadequate early treatment is associated with high rates of dissemination and death. The effects of early diagnosis, dermatologic presentation, and antifungal treatment on outcomes are lacking. CCC cases were reviewed from 2 academic neonatal intensive care units (NICUs) from 2004 to 2015. We defined CCC as a diffuse rash involving the body, extremities, face or scalp, and/or funisitis, presenting in the first week (≤7 days), with identification of Candida species from skin or mucous membrane cultures, and/or by culture or staining of the placenta or umbilical cord. CCC occurred in 0.1% of all NICU admissions (21 of 19 303) and 0.6% of infants <1000 grams birth weight. Median gestational age of CCC infants was 26 3/7 (range, 23 0/7-40 4/7) weeks. Skin findings were commonly present on the day of birth [median (range): 0 (0-6) days], appearing most frequently as a desquamating, maculopapular, papulopustular, and/or erythematous diffuse rash. When systemic antifungal therapy was started empirically at the time of rash presentation and continued for a median (interquartile range) of 14 (14-15) days, all patients survived and none developed dissemination. Delaying systemic treatment, exclusive use of nystatin, and treating for <10 days was associated with Candida bloodstream dissemination. CCC is an invasive infection that presents as a diffuse rash in preterm and term infants. Prompt systemic antifungal treatment at the time of skin presentation for ≥14 days prevents dissemination and Candida-related mortality. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

HIV associated neurocognitive disorders (HAND in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross sectional study.

Directory of Open Access Journals (Sweden)

Christine M Kelly

Full Text Available Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND among patients on combination antiretroviral therapy (cART in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.One hundred and six HIV positive patients, with median (range age 39 (18-71 years, 73% female and median (range CD4 count 323.5 (68-1039 cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]. A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI; however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD nor asymptomatic (ANI forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696 and aOR 0.577 (CI. 0.09, 3.605; p = 0.556 respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and

Comparative and non-comparative studies of the efficacy and tolerance of tioconazole cream 1% versus another imidazole and/or placebo in neonates and infants with candidal diaper rash and/or impetigo.

Science.gov (United States)

Gibbs, D L; Kashin, P; Jevons, S

1987-01-01

Eleven open multicentre studies were conducted to evaluate the efficacy of tioconazole cream 1% as a treatment for diaper rash with or without fungal (Candida) involvement, or impetigo in neonates and infants. In the dermal candidiasis/diaper rash group, 320 patients had either tioconazole (n = 220), a comparative imidazole (n = 43), or vehicle cream (n = 57) applied to the affected area twice daily. Twenty-one impetigo patients had only tioconazole cream 1% applied three times daily to lesions. The overall cure rate (patients with both clinical and mycological cure) at the end of treatment for tioconazole treated patients was 78%, for the comparative imidazole group it was 76% and for vehicle cream it was 39%. At the long-term follow-up evaluation approximately 6 weeks after treatment for patients with diaper rash, the overall cure rate was about the same in both tioconazole- and comparative imidazole-treated patients (87% and 90%, respectively), and 14% in patients using vehicle cream. Side-effects were coincident with disease symptoms and consisted primarily of erythema localized to the treatment area; they occurred in 5.4% (13/241) of the patients who received tioconazole and in 21% (9/43) of the patients who received comparative imidazole (econazole or miconazole). No side-effects were reported in this open study for the 57 patients who used vehicle cream. The results of these studies show that tioconazole cream 1% is safe and effective for the treatment of neonates and infants with dermal candidiasis, diaper rash and impetigo.

Rash impulsiveness and reward sensitivity in relation to risky drinking by university students: potential roles of frontal systems.

Science.gov (United States)

Lyvers, Michael; Duff, Helen; Basch, Vanessa; Edwards, Mark S

2012-08-01

Two forms of impulsivity, rash impulsiveness and reward sensitivity, have been proposed to reflect aspects of frontal lobe functioning and promote substance use. The present study examined these two forms of impulsivity as well as frontal lobe symptoms in relation to risky drinking by university students. University undergraduates aged 18-26years completed the Alcohol Use Disorders Identification Test (AUDIT), Barratt Impulsiveness Scale (BIS-11), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), Frontal Systems Behavior Scale (FrSBe), and a demographics questionnaire assessing age, gender, and age of onset of weekly drinking (AOD). AUDIT-defined harmful drinkers reported earlier AOD and scored higher on BIS-11, the Sensitivity to Reward (SR) scale of the SPSRQ, and the Disinhibition and Executive Dysfunction scales of the FrSBe compared to lower risk groups. Differences remained significant after controlling for duration of alcohol exposure. Path analyses indicated that the influence of SR on AUDIT was mediated by FrSBe Disinhibition, whereas the influence of BIS-11 on AUDIT was mediated by both Disinhibition and Executive Dysfunction scales of the FrSBe. Findings tentatively suggest that the influence of rash impulsiveness on drinking may reflect dysfunction in dorsolateral prefrontal and orbitofrontal systems, whereas the influence of reward sensitivity on drinking may primarily reflect orbitofrontal dysfunction. Irrespective of the underlying functional brain systems involved, results appear to be more consistent with a pre-drinking trait interpretation than effects of alcohol exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

Simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma by liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study

Directory of Open Access Journals (Sweden)

Murali Krishna Matta

2012-10-01

Full Text Available A rapid and sensitive LC–MS/MS method for the simultaneous quantitation of lamivudine, zidovudine and nevirapine in human plasma using abacavir as internal standard has been developed and validated. The analytes and IS were extracted from plasma by solid phase extraction using Oasis HLB cartridges and separated on a Hypurity Advance C18 column using a mixture of acetonitrile:0.1% formic acid (76:24, v/v at a flow rate of 0.8 mL/min. Detection involved an API-4000 LC–MS/MS with electrospray ionization in the positive ion mode and multiple-reaction monitoring for analysis. The method was validated according to FDA guidelines and shown to provide intra- and inter-day precision and accuracy within acceptable limits in a run time of only 3.5 min. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a combination tablet to human male volunteers.

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization.

Science.gov (United States)

Ónodi-Nagy, Katinka; Kinyó, Ágnes; Meszes, Angéla; Garaczi, Edina; Kemény, Lajos; Bata-Csörgő, Zsuzsanna

2015-01-01

It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

Clinical and Laboratory evaluation of measleslike rash in children and young adults

Directory of Open Access Journals (Sweden)

Stewien Klaus Eberhard

2000-01-01

Full Text Available A clinical and laboratory evaluation of 11 children and young adults with measleslike rash was done during the measles outbreak in the Greater São Paulo Metropolitan area at the end of 1996 and spread over the country during 1997. Measles was laboratory confirmed in 07 patients by specific IgM detection in acute serum specimens using an IgM-capture EIA, by specific IgG seroconversion in serum pairs, and by reverse transcription PCR and virus isolation in peripheral blood lymphocytes. Clinical presentations were not always classic; one of the 07 cases had received measles vaccine and corresponded to modified clinical case of measles. The 4 remaining cases were negative for measles and were diagnosed as exanthem subitum (2 cases, scarlet fever and Kawasaki disease. The present study reinforces the view that clinical features alone are not sufficient for establishing an accurate diagnosis in the post-vaccine era, and a surveillance system based on sensitive laboratory results is needed so that it can confirm IgM-negative measles cases.

Risk factors associated with severe scrub typhus in Shandong, northern China.

Science.gov (United States)

Zhang, Luyan; Zhao, Zhongtang; Bi, Zhenwang; Kou, Zengqiang; Zhang, Meng; Yang, Li; Zheng, Li

2014-12-01

The aim of this study was to identify risk factors associated with severe scrub typhus, in order to provide a reference for clinical decision-making. A case-control study was conducted of scrub typhus patients who presented at local hospitals between 2010 and 2013. In total, 46 patients with severe scrub typhus complications (cases) and 194 without severe complications (controls) were included. There were significant differences in the duration of illness before effective antibiotic therapy, lymphadenopathy, rash, blood platelet count, white blood cell (WBC) count, percentage neutrophils, and percentage lymphocytes between the case and control groups. Multivariate analysis demonstrated that the following four factors were significantly associated with the severe complications of scrub typhus: (1) duration of illness before effective antibiotic therapy (odds ratio (OR) 2.287, 95% confidence interval (CI) 1.096-4.770); (2) the presence of a rash (OR 3.694, 95% CI 1.300-10.495); (3) lymphadenopathy (OR 2.438, 95% CI 1.090-5.458); (4) blood platelet count scrub typhus. When scrub typhus patients present with a rash, lymphadenopathy, or blood platelet count <100×10(9)/l, clinicians should be alert to the appearance of severe complications. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genotypic evaluation of etravirine sensitivity of clinical human immunodeficiency virus type 1 (HIV-1) isolates carrying resistance mutations to nevirapine and efavirenz.

Science.gov (United States)

Oumar, A A; Jnaoui, K; Kabamba-Mukadi, B; Yombi, J C; Vandercam, B; Goubau, P; Ruelle, J

2010-01-01

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pattern of resistance mutations quite distinct from the current NNRTIs. We collected all routine samples of HIV-1 patients followed in the AIDS reference laboratory of UCLouvain (in 2006 and 2007) carrying resistance-associated mutations to nevirapine (NVP) or efavirenz (EFV). The sensitivity to Etravirine was estimated using three different drug resistance algorithms: ANRS (July 2008), IAS (December 2008) and Stanford (November 2008). We also verified whether the mutations described as resistance mutations are not due to virus polymorphisms by the study of 58 genotypes of NNRTI-naive patients. Sixty one samples harboured resistance to NVP and EFV: 41/61 had at least one resistance mutation to Etravirine according to ANRS-IAS algorithms; 42/61 samples had at least one resistance mutation to Etravirine according to the Stanford algorithm. 48 and 53 cases were fully sensitive to Etravirine according to ANRS-IAS and Stanford algorithms, respectively. Three cases harboured more than three mutations and presented a pattern of high-degree resistance to Etravirine according to ANRS-IAS algorithm, while one case harboured more than three mutations and presented high degree resistance to Etravirine according to the Stanford algorithm. The V1061 and V179D mutations were more frequent in the ARV-naive group than in the NNRTI-experienced one. According to the currently available algorithms, Etravirine can still be used in the majority of patients with virus showing resistance to NVP and/or EFV, if a combination of other active drugs is included.

Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP.

Science.gov (United States)

Zheng, Xunhai; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

2013-06-18

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Neisseria lactamica Causing a Lung Cavity and Skin Rash in a Renal Transplant Patient: First Report from India

Directory of Open Access Journals (Sweden)

Khalid Hamid Changal

2016-01-01

Full Text Available Neisseria lactamica, a commensal, has been very rarely reported to cause diseases in immunocompromised hosts. In medical literature, there is only one report of a cavitatory lung lesion caused by it. The patient was a kidney transplant recipient. Neisseria lactamica was found to be the cause of his pulmonary cavity and a desquamating rash on feet. With the rapidly spreading medical advance, more and more patients are getting organ transplants, so the population of immunocompromised people is on the rise. We expect more sinister and less expected organisms to cause diseases in patients who have organ transplants.

Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

Science.gov (United States)

Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

2011-01-01

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Morphoea with Myositis: A Rare Association

Directory of Open Access Journals (Sweden)

Mary Sommerlad

2011-01-01

Full Text Available In this case, we describe an unusual presentation of a young woman with a rash typical of morphoea (confirmed on biopsy, who went on to develop myositis in an atypical distribution. Although the association of myositis with diffuse systemic sclerosis is well described, the link with localised scleroderma (morphoea and myositis has not been described.

LDAP: a web server for lncRNA-disease association prediction.

Science.gov (United States)

Lan, Wei; Li, Min; Zhao, Kaijie; Liu, Jin; Wu, Fang-Xiang; Pan, Yi; Wang, Jianxin

2017-02-01

Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in many human diseases. Therefore, predicting novel lncRNA-disease associations would contribute to dissect the complex mechanisms of disease pathogenesis. Some computational methods have been developed to infer lncRNA-disease associations. However, most of these methods infer lncRNA-disease associations only based on single data resource. In this paper, we propose a new computational method to predict lncRNA-disease associations by integrating multiple biological data resources. Then, we implement this method as a web server for lncRNA-disease association prediction (LDAP). The input of the LDAP server is the lncRNA sequence. The LDAP predicts potential lncRNA-disease associations by using a bagging SVM classifier based on lncRNA similarity and disease similarity. The web server is available at http://bioinformatics.csu.edu.cn/ldap jxwang@mail.csu.edu.cn. Supplementary data are available at Bioinformatics online.

Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

Science.gov (United States)

Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

2016-03-16

Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

Neural Inductive Matrix Completion for Predicting Disease-Gene Associations

KAUST Repository

Hou, Siqing

2018-05-21

In silico prioritization of undiscovered associations can help find causal genes of newly discovered diseases. Some existing methods are based on known associations, and side information of diseases and genes. We exploit the possibility of using a neural network model, Neural inductive matrix completion (NIMC), in disease-gene prediction. Comparing to the state-of-the-art inductive matrix completion method, using neural networks allows us to learn latent features from non-linear functions of input features. Previous methods use disease features only from mining text. Comparing to text mining, disease ontology is a more informative way of discovering correlation of dis- eases, from which we can calculate the similarities between diseases and help increase the performance of predicting disease-gene associations. We compare the proposed method with other state-of-the-art methods for pre- dicting associated genes for diseases from the Online Mendelian Inheritance in Man (OMIM) database. Results show that both new features and the proposed NIMC model can improve the chance of recovering an unknown associated gene in the top 100 predicted genes. Best results are obtained by using both the new features and the new model. Results also show the proposed method does better in predicting associated genes for newly discovered diseases.

Fatal toxic epidermal necrolysis associated with minoxidil.

Science.gov (United States)

Karaoui, Lamis R; Chahine-Chakhtoura, Corinne

2009-04-01

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this

Is lower symptom recognition associated with socioeconomic inequalities in help-seeking for potential breast cancer symptoms?

Science.gov (United States)

Davies, Hilary; Marcu, Afrodita; Vedsted, Peter; Whitaker, Katriina L

2018-02-01

Socioeconomic inequalities in recognising signs and symptoms of cancer may result in inequalities in timely help-seeking and subsequent prognosis of breast cancer. We explored the mediating role of symptom attribution and concern on the relationship between level of education and help-seeking for potential breast cancer symptoms. Women aged ≥47 years (n = 961) were purposively recruited (by education) to complete an online vignette-based survey that included nipple rash and axillary lump (in separate vignettes) as potential symptoms of breast cancer. Women completed questions relating to medical help-seeking (yes/no), cancer attribution, symptom concern, cancer avoidance, family history, and demographics. Women with low education and mid education attributed nipple rash less often to cancer (26% and 27% mentioned cancer) than women with a degree or higher (40%). However, women with a degree or higher (63%) or mid education (64%) were less likely to anticipate seeking help for the nipple rash than women with no formal qualifications (73%). This association was statistically significant in the 60- to 69-year-old age group. There was no significant association between education and help-seeking for axillary lump. Mediation analysis adjusting for potential confounders confirmed that the association between education and help-seeking for nipple rash was fully mediated by symptom concern. Socioeconomic inequalities in stage at diagnosis and survival of breast cancer may not always be explained by lower likelihood of suspecting cancer and subsequent impact on help-seeking. Reducing inequalities in stage at diagnosis will involve understanding a broader range of bio-psycho-social factors (eg, comorbidities and healthcare system factors). Copyright © 2017 John Wiley & Sons, Ltd.

Ventromedial Prefrontal Cortex Activation Is Associated with Memory Formation for Predictable Rewards

Science.gov (United States)

Bialleck, Katharina A.; Schaal, Hans-Peter; Kranz, Thorsten A.; Fell, Juergen; Elger, Christian E.; Axmacher, Nikolai

2011-01-01

During reinforcement learning, dopamine release shifts from the moment of reward consumption to the time point when the reward can be predicted. Previous studies provide consistent evidence that reward-predicting cues enhance long-term memory (LTM) formation of these items via dopaminergic projections to the ventral striatum. However, it is less clear whether memory for items that do not precede a reward but are directly associated with reward consumption is also facilitated. Here, we investigated this question in an fMRI paradigm in which LTM for reward-predicting and neutral cues was compared to LTM for items presented during consumption of reliably predictable as compared to less predictable rewards. We observed activation of the ventral striatum and enhanced memory formation during reward anticipation. During processing of less predictable as compared to reliably predictable rewards, the ventral striatum was activated as well, but items associated with less predictable outcomes were remembered worse than items associated with reliably predictable outcomes. Processing of reliably predictable rewards activated the ventromedial prefrontal cortex (vmPFC), and vmPFC BOLD responses were associated with successful memory formation of these items. Taken together, these findings show that consumption of reliably predictable rewards facilitates LTM formation and is associated with activation of the vmPFC. PMID:21326612

Association of psychological stress with skin symptoms among medical students

Directory of Open Access Journals (Sweden)

Ghada A. Bin Saif

2018-01-01

Full Text Available Objectives: To evaluate the association between psychological stress and skin symptoms among medical students. Methods: A cross-sectional study was carried out between January and June 2015. Electronic survey consists of Perceived Stress Questionnaire (PSQ and Self-Reported Skin Complaints Questionnaire were distributed to all 1435 undergraduate students at College of Medicine, King Saud University (KSU, Riyadh, Saudi Arabia. Results: Final analysis was performed on data from 529 (36.9% students. Students were divided into three groups: least stressed students, n=135, PSQ index less than 0.39; highly stressed students, n=136, PSQ index greater than 0.61; and moderately stressed students, n=258. Older age, female gender, during exam weeks, and fourth and fifth years of medical school (all p less than 0.01 were associated with the highest perceived stress levels. When compared to least stressed students, highly stressed students suffered from more oily, waxy patches or flakes on scalp (p≤0.0001, dry/sore rash (p≤0.0001, warts (p≤0.0001, pimples (p≤0.0001, itchy skin (p≤0.0001, hands itchy rash (p≤0.0001, hair loss (p≤0.0001, pull-out own hair (p=0.008, scaly skin (p=0.012, troublesome sweating (p=0.016, nails biting (p=0.028, and other rashes on face (p= 0.028. Conclusion: Various common skin conditions could appear in context of psychological stress among medical students.

Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.

Science.gov (United States)

Troyanov, Yves; Targoff, Ira N; Payette, Marie-Pier; Raynauld, Jean-Pierre; Chartier, Suzanne; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Rich, Eric; Grodzicky, Tamara; Fritzler, Marvin J; Joyal, France; Koenig, Martial; Senécal, Jean-Luc

2014-11-01

cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.

HAMDA: Hybrid Approach for MiRNA-Disease Association prediction.

Science.gov (United States)

Chen, Xing; Niu, Ya-Wei; Wang, Guang-Hui; Yan, Gui-Ying

2017-12-01

For decades, enormous experimental researches have collectively indicated that microRNA (miRNA) could play indispensable roles in many critical biological processes and thus also the pathogenesis of human complex diseases. Whereas the resource and time cost required in traditional biology experiments are expensive, more and more attentions have been paid to the development of effective and feasible computational methods for predicting potential associations between disease and miRNA. In this study, we developed a computational model of Hybrid Approach for MiRNA-Disease Association prediction (HAMDA), which involved the hybrid graph-based recommendation algorithm, to reveal novel miRNA-disease associations by integrating experimentally verified miRNA-disease associations, disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity into a recommendation algorithm. HAMDA took not only network structure and information propagation but also node attribution into consideration, resulting in a satisfactory prediction performance. Specifically, HAMDA obtained AUCs of 0.9035 and 0.8395 in the frameworks of global and local leave-one-out cross validation, respectively. Meanwhile, HAMDA also achieved good performance with AUC of 0.8965 ± 0.0012 in 5-fold cross validation. Additionally, we conducted case studies about three important human cancers for performance evaluation of HAMDA. As a result, 90% (Lymphoma), 86% (Prostate Cancer) and 92% (Kidney Cancer) of top 50 predicted miRNAs were confirmed by recent experiment literature, which showed the reliable prediction ability of HAMDA. Copyright © 2017 Elsevier Inc. All rights reserved.

GIMDA: Graphlet interaction-based MiRNA-disease association prediction.

Science.gov (United States)

Chen, Xing; Guan, Na-Na; Li, Jian-Qiang; Yan, Gui-Ying

2018-03-01

MicroRNAs (miRNAs) have been confirmed to be closely related to various human complex diseases by many experimental studies. It is necessary and valuable to develop powerful and effective computational models to predict potential associations between miRNAs and diseases. In this work, we presented a prediction model of Graphlet Interaction for MiRNA-Disease Association prediction (GIMDA) by integrating the disease semantic similarity, miRNA functional similarity, Gaussian interaction profile kernel similarity and the experimentally confirmed miRNA-disease associations. The related score of a miRNA to a disease was calculated by measuring the graphlet interactions between two miRNAs or two diseases. The novelty of GIMDA lies in that we used graphlet interaction to analyse the complex relationships between two nodes in a graph. The AUCs of GIMDA in global and local leave-one-out cross-validation (LOOCV) turned out to be 0.9006 and 0.8455, respectively. The average result of five-fold cross-validation reached to 0.8927 ± 0.0012. In case study for colon neoplasms, kidney neoplasms and prostate neoplasms based on the database of HMDD V2.0, 45, 45, 41 of the top 50 potential miRNAs predicted by GIMDA were validated by dbDEMC and miR2Disease. Additionally, in the case study of new diseases without any known associated miRNAs and the case study of predicting potential miRNA-disease associations using HMDD V1.0, there were also high percentages of top 50 miRNAs verified by the experimental literatures. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Critical evidence for the prediction error theory in associative learning.

Science.gov (United States)

Terao, Kanta; Matsumoto, Yukihisa; Mizunami, Makoto

2015-03-10

In associative learning in mammals, it is widely accepted that the discrepancy, or error, between actual and predicted reward determines whether learning occurs. Complete evidence for the prediction error theory, however, has not been obtained in any learning systems: Prediction error theory stems from the finding of a blocking phenomenon, but blocking can also be accounted for by other theories, such as the attentional theory. We demonstrated blocking in classical conditioning in crickets and obtained evidence to reject the attentional theory. To obtain further evidence supporting the prediction error theory and rejecting alternative theories, we constructed a neural model to match the prediction error theory, by modifying our previous model of learning in crickets, and we tested a prediction from the model: the model predicts that pharmacological intervention of octopaminergic transmission during appetitive conditioning impairs learning but not formation of reward prediction itself, and it thus predicts no learning in subsequent training. We observed such an "auto-blocking", which could be accounted for by the prediction error theory but not by other competitive theories to account for blocking. This study unambiguously demonstrates validity of the prediction error theory in associative learning.

A 6-year-old girl with fever, rash, and increased intracranial pressure.

Science.gov (United States)

Ravish, Matthew E; Krowchuk, Daniel P; Zapadka, Michael; Shetty, Avinash K

2013-08-01

Rocky Mountain spotted fever (RMSF) is a well-described, potentially lethal, tick-borne zoonotic infection and has very effective therapy. However, the diagnosis might not be made early enough, often leading to worse outcomes. Our aim was to discuss the diagnostic dilemmas facing the physician when evaluating patients with suspected RMSF. We report a case of RMSF in a 6-year-old girl who presented to our hospital with a 7-day history of fever, headache, and a petechial rash. After blood cultures were obtained, the patient was treated empirically with doxycycline, vancomycin, and ceftriaxone. During the next 24 h, her clinical status worsened, with acute onset of altered mental status, posturing, and fixed and dilated pupils. A computed tomography scan of the brain demonstrated diffuse cerebral edema with evidence of tonsillar herniation. She died 24 h after admission. A serum specimen tested positive for immunoglobulin G to Rickettsia rickettsii at a titer of 128 dilutions, confirming recent infection. We present this case to raise awareness of RMSF in patients who present with a nonspecific febrile illness in tick-endemic areas in the United States. Early diagnosis and treatment with doxycycline before day 5 of illness is essential and can prevent morbidity and mortality. Copyright © 2013 Elsevier Inc. All rights reserved.

A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients.

Science.gov (United States)

Suleiman, Ahmed Abbas; Frechen, Sebastian; Scheffler, Matthias; Zander, Thomas; Nogova, Lucia; Kocher, Martin; Jaehde, Ulrich; Wolf, Jürgen; Fuhr, Uwe

2015-11-01

Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE). We present a modeling and simulation framework for the most common erlotinib-induced AE, rash, and diarrhea, providing insights into erlotinib toxicity. We used the framework to investigate the safety of high-dose erlotinib pulses proposed to limit acquired resistance while treating NSCLC. Continuous-time Markov models were developed using rash and diarrhea AE data from 39 NSCLC patients treated with erlotinib (150 mg/day). Exposure and different covariates were investigated as predictors of variability. Rash was also tested as a survival predictor. Models developed were used in a simulation analysis to compare the toxicities of different regimens, including the previously mentioned pulsed strategy. Probabilities of experiencing rash or diarrhea were found to be highest early during treatment. Rash, but not diarrhea, was positively correlated with erlotinib exposure. In contrast with some common understandings, radiotherapy decreased transitioning to higher rash grades by 81% (p simulations predicted that the proposed pulsed regimen (1600 mg/week + 50 mg/day remaining week days) results in a maximum of 20% of the patients suffering from severe rash throughout the treatment course in comparison to 12% when treated with standard dosing (150 mg/day). In conclusion, the framework demonstrated that radiotherapy attenuates erlotinib-induced rash, providing an opportunity to use radiotherapy and erlotinib together, and demonstrated the tolerability of high-dose pulses intended to address acquired resistance to erlotinib.

Inductive matrix completion for predicting gene-disease associations.

Science.gov (United States)

Natarajan, Nagarajan; Dhillon, Inderjit S

2014-06-15

Most existing methods for predicting causal disease genes rely on specific type of evidence, and are therefore limited in terms of applicability. More often than not, the type of evidence available for diseases varies-for example, we may know linked genes, keywords associated with the disease obtained by mining text, or co-occurrence of disease symptoms in patients. Similarly, the type of evidence available for genes varies-for example, specific microarray probes convey information only for certain sets of genes. In this article, we apply a novel matrix-completion method called Inductive Matrix Completion to the problem of predicting gene-disease associations; it combines multiple types of evidence (features) for diseases and genes to learn latent factors that explain the observed gene-disease associations. We construct features from different biological sources such as microarray expression data and disease-related textual data. A crucial advantage of the method is that it is inductive; it can be applied to diseases not seen at training time, unlike traditional matrix-completion approaches and network-based inference methods that are transductive. Comparison with state-of-the-art methods on diseases from the Online Mendelian Inheritance in Man (OMIM) database shows that the proposed approach is substantially better-it has close to one-in-four chance of recovering a true association in the top 100 predictions, compared to the recently proposed Catapult method (second best) that has bigdata.ices.utexas.edu/project/gene-disease. © The Author 2014. Published by Oxford University Press.

Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash

DEFF Research Database (Denmark)

Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole

2017-01-01

PURPOSE: Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated...... the effect of a vitamin K3 cream on cetuximab-induced rash. MATERIALS AND METHODS: Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream...... stained for EGFR and pEGFR. RESULTS: Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed...

Nanoparticles-cell association predicted by protein corona fingerprints

Science.gov (United States)

Palchetti, S.; Digiacomo, L.; Pozzi, D.; Peruzzi, G.; Micarelli, E.; Mahmoudi, M.; Caracciolo, G.

2016-06-01

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a ``protein corona'' layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ~ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells.In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a ``protein corona'' layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ~ 100-250 nm) and surface

Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana

Directory of Open Access Journals (Sweden)

Kathleen M. Powis

2018-03-01

Full Text Available Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV or nevirapine (NVP prophylaxis for the prevention of intrapartum motherto-child HIV transmission (MTCT among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants.   Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation, with a birth weight ≥ 2500 g and who were formula-fed from birth. ZDV infant prophylaxis was used from Mpepu Study inception. A protocol modification mid-way through the study led to the subsequent use of NVP infant prophylaxis.   Results: Among infants qualifying for this secondary retrospective analysis, a total of 695 (52% infants received ZDV, while 646 (48% received NVP from birth for at least 25 days but no more than 35 days. Confirmed intrapartum HIV infection occurred in two (0.29% ZDV recipients and three (0.46% NVP recipients (p = 0.68. Anaemia occurred in 19 (2.7% ZDV versus 12 (1.9% NVP (p = 0.36 recipients. Neutropenia occurred in 28 (4.0% ZDV versus 21 (3.3% NVP recipients (p = 0.47.   Conclusions: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4 among formula-fed full-term infants with a birthweight ≥ 2500 g.

Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.

Science.gov (United States)

Matteelli, Alberto; Saleri, Nuccia; Villani, Paola; Bonkoungou, Victor; Carvalho, Anna Cristina C; Kouanda, Seni; Sanou, Marie J; Simporé, Jacques; Monno, Laura; Carosi, Giampiero; Regazzi, Mario; Dembele, Mathurin

2009-09-01

Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. HIV-1-infected patients with CD4+ T-lymphocyte count

Association with humans and seasonality interact to reverse predictions for animal space use.

Science.gov (United States)

Laver, Peter N; Alexander, Kathleen A

2018-01-01

Variation in animal space use reflects fitness trade-offs associated with ecological constraints. Associated theories such as the metabolic theory of ecology and the resource dispersion hypothesis generate predictions about what drives variation in animal space use. But, metabolic theory is usually tested in macro-ecological studies and is seldom invoked explicitly in within-species studies. Full evaluation of the resource dispersion hypothesis requires testing in more species. Neither have been evaluated in the context of anthropogenic landscape change. In this study, we used data for banded mongooses ( Mungos mungo ) in northeastern Botswana, along a gradient of association with humans, to test for effects of space use drivers predicted by these theories. We used Bayesian parameter estimation and inference from linear models to test for seasonal differences in space use metrics and to model seasonal effects of space use drivers. Results suggest that space use is strongly associated with variation in the level of overlap that mongoose groups have with humans. Seasonality influences this association, reversing seasonal space use predictions historically-accepted by ecologists. We found support for predictions of the metabolic theory when moderated by seasonality, by association with humans and by their interaction. Space use of mongooses living in association with humans was more concentrated in the dry season than the wet season, when historically-accepted ecological theory predicted more dispersed space use. Resource richness factors such as building density were associated with space use only during the dry season. We found negligible support for predictions of the resource dispersion hypothesis in general or for metabolic theory where seasonality and association with humans were not included. For mongooses living in association with humans, space use was not associated with patch dispersion or group size over both seasons. In our study, living in association

Refractory priapism associated with ingestion of yohimbe extract

OpenAIRE

Myers, Amy; Barrueto, Fermin

2009-01-01

Extracts of the bark of the central African treePausinystalia yohimbe contain yohimbine, an indole alkaloid, which is used to treat erectile dysfunction. The reported side effects of over-the-counter preparations of yohimbine include gastrointestinal upset, anxiety, increased blood pressure, headache, agitation, rash, tachycardia, and frequent urination. In this report, we describe a severe case of intractable priapism associated with the ingestion of yohimbe extract. Management required inse...

Association Rule-based Predictive Model for Machine Failure in Industrial Internet of Things

Science.gov (United States)

Kwon, Jung-Hyok; Lee, Sol-Bee; Park, Jaehoon; Kim, Eui-Jik

2017-09-01

This paper proposes an association rule-based predictive model for machine failure in industrial Internet of things (IIoT), which can accurately predict the machine failure in real manufacturing environment by investigating the relationship between the cause and type of machine failure. To develop the predictive model, we consider three major steps: 1) binarization, 2) rule creation, 3) visualization. The binarization step translates item values in a dataset into one or zero, then the rule creation step creates association rules as IF-THEN structures using the Lattice model and Apriori algorithm. Finally, the created rules are visualized in various ways for users’ understanding. An experimental implementation was conducted using R Studio version 3.3.2. The results show that the proposed predictive model realistically predicts machine failure based on association rules.

[Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

Science.gov (United States)

Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

2009-10-01

Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

Energy Technology Data Exchange (ETDEWEB)

Caba, Octavio, E-mail: ocaba@ujaen.es [Department of Health Sciences, University of Jaen, Jaen (Spain); Irigoyen, Antonio, E-mail: antonioirigoyen@yahoo.com [Department of Medical Oncology, Virgen de la Salud Hospital, Toledo (Spain); Jimenez-Luna, Cristina, E-mail: crisjilu@ugr.es [Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada (Spain); Benavides, Manuel, E-mail: manuel.benavides.sspa@juntadeandalucia.es [Department of Medical Oncology, Virgen de la Victoria Hospital, Malaga (Spain); Ortuño, Francisco M., E-mail: fortuno@ugr.es [Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada (Spain); Gallego, Javier, E-mail: j.gallegoplazas@gmail.com [Department of Medical Oncology, General Universitario de Elche Hospital, Alicante (Spain); Rojas, Ignacio, E-mail: irojas@ugr.es [Department of Computer Architecture and Computer Technology, Research Center for Information and Communications Technologies, University of Granada, Granada (Spain); Guillen-Ponce, Carmen, E-mail: carmen.guillen@salud.madrid.org [Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid (Spain); Torres, Carolina, E-mail: ctorres@uic.edu [Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL (United States); Aranda, Enrique, E-mail: enrique.aranda@imibic.org [Maimonides Institute of Biomedical Research (IMIBIC), Reina Sofía Hospital, University of Córdoba, Córdoba (Spain); Prados, Jose, E-mail: jcprados@ugr.es [Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada (Spain)

2016-11-15

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21 patients developed any grade of SR, while 13 patients did not (controls). Before administering any chemotherapy regimen and the development of SR, we collected RNA from peripheral blood samples of all patients and studied the differential gene expression pattern using the Illumina microarray platform HumanHT-12 v4 Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10, and SIAH2), involved in different pathways including regulatory, migratory, and signalling processes, were downregulated in PDAC patients with SR. Our results suggest the existence of a gene expression profiling significantly correlated with erlotinib-induced SR in PDAC that could be used as prognostic indicator in this patients. - Highlights: • Skin rash (SR) is the most characteristic side effect of erlotinib in PDAC patients. • Erlotinib-induced SR has been associated with a better clinical outcome. • Gene expression profiling was used to determine who will develop this manifestation. • 7 genes involved in different pathways were downregulated in PDAC patients with SR. • Our profile correlated with erlotinib-induced SR in PDAC could be used for prognosis.

Risk Prediction Using Genome-Wide Association Studies on Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Sungkyoung Choi

2016-12-01

Full Text Available The success of genome-wide association studies (GWASs has enabled us to improve risk assessment and provide novel genetic variants for diagnosis, prevention, and treatment. However, most variants discovered by GWASs have been reported to have very small effect sizes on complex human diseases, which has been a big hurdle in building risk prediction models. Recently, many statistical approaches based on penalized regression have been developed to solve the “large p and small n” problem. In this report, we evaluated the performance of several statistical methods for predicting a binary trait: stepwise logistic regression (SLR, least absolute shrinkage and selection operator (LASSO, and Elastic-Net (EN. We first built a prediction model by combining variable selection and prediction methods for type 2 diabetes using Affymetrix Genome-Wide Human SNP Array 5.0 from the Korean Association Resource project. We assessed the risk prediction performance using area under the receiver operating characteristic curve (AUC for the internal and external validation datasets. In the internal validation, SLR-LASSO and SLR-EN tended to yield more accurate predictions than other combinations. During the external validation, the SLR-SLR and SLR-EN combinations achieved the highest AUC of 0.726. We propose these combinations as a potentially powerful risk prediction model for type 2 diabetes.

Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

Science.gov (United States)

Kurbel, Beatrica; Golem, Ante Zvonimir; Kurbel, Sven

2015-01-01

Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

Predictive features associated with thyrotoxic storm and management.

Science.gov (United States)

Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Guzzetti, Luca; De Martino, Alessandro Ivan; Severgnini, Paolo; Cuffari, Salvatore

2017-10-01

Thyroid storm (TS) is an endocrine emergency characterized by rapid deterioration, associated with high mortality rate therefore rapid diagnosis and emergent treatment is mandatory. In the past, thyroid surgery was the most common cause of TS, but recent preoperative medication creates a euthyroid state before performing surgery. An active approach during perioperative period could determine an effective clinical treatment of this life-threating diseases. Recently, the Japan Thyroid Association and Japan Endocrine Society developed diagnostic criteria for TS focusing on premature and prompt diagnosis avoiding inopportune e useless drugs. This review analyses predictive features associated with thyrotoxic storm highlighting recent literature to optimize the patient quality of care.

New insights into systemic amyloidosis: primary amyloidosis associated with tubercular lymphadenitis

Directory of Open Access Journals (Sweden)

Shivraj Meena, Nirmal Ghati, Rita Sood, Naval Kishore Vikram

2014-11-01

Full Text Available Tuberculosis is generally followed by secondary amyloidosis. The association of primary systemic amyloidosis with tuberculosis is very rare. There is only one case thus far reported in literature. We report such a rare case of primary amyloidosis with tuberculous lymphadenopathy. A 45 year old woman presented at the medicine department of all India institute of medical sciences , New Delhi with on & off erythematous rashes over both eyes for 1 year; low grade fever, fatigue and significant weight loss for 4 months, dysphagia for solid food since 1 month. Main finding on examination were pallor, macroglossia, bilateral periorbital erythematous rashes (racoon eyes, hepatomegaly & cardiomegaly. She had raised serum alkaline phosphatase level. Chest x-ray revealed cardiomegaly. USG abdomen revealed multiple retroperitoneal mesenteric lymph nodes and hepatomegaly. USG guided FNAC from mesenteric lymph node showed acid fast bacillus. Histological examination of liver biopsy showed amyloid deposition on congo red stain. Patient was treated with DOTS category I ATT with Bortezomib and Dexamethasone based weekly chemotherapy.

Analysis of nevirapine (NVP) resistance in Ugandan infants who were HIV infected despite receiving single-Dose (SD) NVP versus SD NVP plus daily NVP up to 6 weeks of age to prevent HIV vertical transmission.

Science.gov (United States)

Church, Jessica D; Omer, Saad B; Guay, Laura A; Huang, Wei; Lidstrom, Jessica; Musoke, Philippa; Mmiro, Francis; Jackson, J Brooks; Eshleman, Susan H

2008-10-01

Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Analysis of a Shock-Associated Noise Prediction Model Using Measured Jet Far-Field Noise Data

Science.gov (United States)

Dahl, Milo D.; Sharpe, Jacob A.

2014-01-01

A code for predicting supersonic jet broadband shock-associated noise was assessed using a database containing noise measurements of a jet issuing from a convergent nozzle. The jet was operated at 24 conditions covering six fully expanded Mach numbers with four total temperature ratios. To enable comparisons of the predicted shock-associated noise component spectra with data, the measured total jet noise spectra were separated into mixing noise and shock-associated noise component spectra. Comparisons between predicted and measured shock-associated noise component spectra were used to identify deficiencies in the prediction model. Proposed revisions to the model, based on a study of the overall sound pressure levels for the shock-associated noise component of the measured data, a sensitivity analysis of the model parameters with emphasis on the definition of the convection velocity parameter, and a least-squares fit of the predicted to the measured shock-associated noise component spectra, resulted in a new definition for the source strength spectrum in the model. An error analysis showed that the average error in the predicted spectra was reduced by as much as 3.5 dB for the revised model relative to the average error for the original model.

Predicting College Students' Positive Psychology Associated Traits with Executive Functioning Dimensions

Science.gov (United States)

Marshall, Seth

2016-01-01

More research is needed that investigates how positive psychology-associated traits are predicted by neurocognitive processes. Correspondingly, the purpose of this study was to ascertain how, and to what extent, four traits, namely, grit, optimism, positive affect, and life satisfaction were predicted by the executive functioning (EF) dimensions…

In silico prediction of novel therapeutic targets using gene-disease association data.

Science.gov (United States)

Ferrero, Enrico; Dunham, Ian; Sanseau, Philippe

2017-08-29

Target identification and validation is a pressing challenge in the pharmaceutical industry, with many of the programmes that fail for efficacy reasons showing poor association between the drug target and the disease. Computational prediction of successful targets could have a considerable impact on attrition rates in the drug discovery pipeline by significantly reducing the initial search space. Here, we explore whether gene-disease association data from the Open Targets platform is sufficient to predict therapeutic targets that are actively being pursued by pharmaceutical companies or are already on the market. To test our hypothesis, we train four different classifiers (a random forest, a support vector machine, a neural network and a gradient boosting machine) on partially labelled data and evaluate their performance using nested cross-validation and testing on an independent set. We then select the best performing model and use it to make predictions on more than 15,000 genes. Finally, we validate our predictions by mining the scientific literature for proposed therapeutic targets. We observe that the data types with the best predictive power are animal models showing a disease-relevant phenotype, differential expression in diseased tissue and genetic association with the disease under investigation. On a test set, the neural network classifier achieves over 71% accuracy with an AUC of 0.76 when predicting therapeutic targets in a semi-supervised learning setting. We use this model to gain insights into current and failed programmes and to predict 1431 novel targets, of which a highly significant proportion has been independently proposed in the literature. Our in silico approach shows that data linking genes and diseases is sufficient to predict novel therapeutic targets effectively and confirms that this type of evidence is essential for formulating or strengthening hypotheses in the target discovery process. Ultimately, more rapid and automated target

Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa.

Science.gov (United States)

Goodall, Ruth L; Dunn, David T; Nkurunziza, Peter; Mugarura, Lincoln; Pattery, Theresa; Munderi, Paula; Kityo, Cissy; Gilks, Charles; Kaleebu, Pontiano; Pillay, Deenan; Gupta, Ravindra K

2017-05-01

Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P  =   0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P  =   0.18). Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

[Predictive factors associated with severity of asthma exacerbations].

Science.gov (United States)

Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

2008-01-01

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Refractory priapism associated with ingestion of yohimbe extract.

Science.gov (United States)

Myers, Amy; Barrueto, Fermin

2009-12-01

Extracts of the bark of the central African tree Pausinystalia yohimbe contain yohimbine, an indole alkaloid, which is used to treat erectile dysfunction. The reported side effects of over-the-counter preparations of yohimbine include gastrointestinal upset, anxiety, increased blood pressure, headache, agitation, rash, tachycardia, and frequent urination. In this report, we describe a severe case of intractable priapism associated with the ingestion of yohimbe extract. Management required insertion of a proximal cavernosal spongiosum shunt (Quackles shunt) in the operating room.

Reuse of single-dose nevirapine in subsequent pregnancies for the prevention of mother-to-child HIV transmission in Lusaka, Zambia: A cohort study

Directory of Open Access Journals (Sweden)

Sinkala Moses

2008-12-01

Full Text Available Abstract Background Single-dose nevirapine (SDNVP for the prevention of mother-to-child HIV transmission (PMTCT results in the selection of resistance mutants among HIV-infected mothers. The effects of these mutations on the efficacy of SDNVP use in a subsequent pregnancy are not well understood. Methods We compared risks of perinatal HIV transmission between multiparous women who had previously received a dose of SDNVP (exposed and those that had not (unexposed and who were given SDNVP for the index pregnancy within a PMTCT clinical study. We also compared transmission risks among exposed and unexposed women who had two consecutive pregnancies within the trial. Logistic regression modeling was used to adjust for possible confounders. Results Transmission risks did not differ between 59 SDNVP-exposed and 782 unexposed women in unadjusted analysis or after adjustment for viral load and disease stage (adjusted odds ratio 0.6, 95% confidence interval [CI] 0.2 to 2.0. Among 43 women who had two consecutive pregnancies during the study, transmission risks were 7% (95% CI 1% to 19% at both the first (unexposed and second (exposed delivery. The results were unchanged, if infant death was included as an outcome. Conclusion These data suggest that the efficacy of SDNVP may not be diminished when reused in subsequent pregnancies.

Low rate of mother-to-child transmission of HIV-1 after nevirapine intervention in a pilot public health program in Yaoundé, Cameroon.

Science.gov (United States)

Ayouba, Ahidjo; Tene, Gilbert; Cunin, Patrick; Foupouapouognigni, Yacouba; Menu, Elisabeth; Kfutwah, Anfumbom; Thonnon, Jocelyn; Scarlatti, Gabriella; Monny-Lobé, Marcel; Eteki, Nicole; Kouanfack, Charles; Tardy, Michèle; Leke, Robert; Nkam, Maurice; Nlend, Anne E; Barré-Sinoussi, Françoise; Martin, Paul M V; Nerrienet, Eric

2003-11-01

To determine the percentage of infected children for whom nevirapine (NVP) was used to prevent peripartum mother-to-child transmission (MTCT) of HIV in Yaoundé, Cameroon. The study was a prospective Public Health Pilot Program covering a 3-year period (January 2000-December 2002). Counseled and consenting HIV-1-positive pregnant women were given a single dose of NVP at the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours of life. NVP-treated children were regularly followed up and examined for HIV-1 infection at 6-8 weeks and 5-6 months through plasma viral load (VL) quantification with the bDNA system. One hundred twenty-three children were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months. Thirteen children (10.6% [13/123]; 95% confidence interval, 5.1-16) were infected and presented with high VLs, in general >500,000 copies/mL. Two children had intermediate VLs (between 50 and 3500 copies/mL) at both time points. One hundred seven children (87%) were considered not infected at 6-8 weeks of age. Our results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP administration was not >13% (16/123), thus demonstrating the effectiveness of NVP for lowering the risk of HIV-1 MTCT in real-life settings.

Predicting exposure-response associations of ambient particulate matter with mortality in 73 Chinese cities

International Nuclear Information System (INIS)

Madaniyazi, Lina; Guo, Yuming; Chen, Renjie; Kan, Haidong; Tong, Shilu

2016-01-01

Estimating the burden of mortality associated with particulates requires knowledge of exposure-response associations. However, the evidence on exposure-response associations is limited in many cities, especially in developing countries. In this study, we predicted associations of particulates smaller than 10 μm in aerodynamic diameter (PM_1_0) with mortality in 73 Chinese cities. The meta-regression model was used to test and quantify which city-specific characteristics contributed significantly to the heterogeneity of PM_1_0-mortality associations for 16 Chinese cities. Then, those city-specific characteristics with statistically significant regression coefficients were treated as independent variables to build multivariate meta-regression models. The model with the best fitness was used to predict PM_1_0-mortality associations in 73 Chinese cities in 2010. Mean temperature, PM_1_0 concentration and green space per capita could best explain the heterogeneity in PM_1_0-mortality associations. Based on city-specific characteristics, we were able to develop multivariate meta-regression models to predict associations between air pollutants and health outcomes reasonably well. - Highlights: • The heterogeneity was examined in PM_1_0-mortality associations among Chinese cities. • Temperature, PM_1_0 and green space could best explain the heterogeneity. • PM_1_0-mortality associations were predicted for 73 Chinese cities. - This study provides a practical way to assess exposure-response associations and evaluate the burden of mortality in areas with insufficient data.

Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

Science.gov (United States)

Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

2017-12-01

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Incidence of nevirapine-associated hepatitis in an antenatal clinic ...

African Journals Online (AJOL)

based highly active antiretroviral therapy at a dedicated antenatal antiretroviral clinic between July 2004 and December 2006. Results. Three hundred and ninety women were included in the analysis. Median age was 29 (interquartile range (IQR)

Dermatologic adverse events associated with chemotherapy and targeted anticancer therapy

Directory of Open Access Journals (Sweden)

Maria Kowalska

2016-05-01

Full Text Available Chemotherapeutic agents and drugs used for targeted tumor therapy often cause undesirable side effects of the skin which typically are toxic cutaneous reactions (toxicity grade 1 to 4. The first group of drugs that cause toxicities affecting the skin are inhibitors of epidermal growth factor receptor (EGFR. They cause a variety of skin changes (PRIDE syndrome, which are mainly manifested by papulopustular rash, also referred to as acneiform rash, occurring in 44–74% of patients. Another drug which causes cutaneous toxicities is inhibitor of CTLA4 (cytotoxic T lymphocyte-associated protein 4, which is represented by ipilimumab, used in the treatment of metastatic melanoma. The most common dermatological adverse event, observed in 40–64% of patients receiving ipilimumab, is generalized maculopapular rash with pruritus and dry skin, and in some cases vitiligo is also observed. BRAF and MEK inhibitors introduced for the treatment of advanced melanoma also cause skin rashes. BRAF inhibitors also affecting the proliferation of keratinocytes stimulate hypertrophic changes and cause the whole spectrum of lesions from benign and keratoacanthoma to squamous cell carcinoma. A hedgehog pathway inhibitor (vismodegib is used for the treatment of metastatic basal cell carcinoma. The most common adverse events it causes are reversible alopecia and dysgeusia, but it can also cause the development of keratoacanthoma and squamous cell carcinoma. Among the most common side effects of chemotherapy and targeted therapy are toxic changes within the hands and feet (hand-foot skin reaction – HFSR that early manifest as a neurological symptoms (numbness, paresthesia, and skin symptoms (erythematous swelling changes, blisters, hyperkeratosis occur later. Anti-cancer drugs can also cause serious skin diseases such as Stevens-Johnson syndrome (SJS, toxic epidermal necrolysis (TEN and DRESS (drug rash with eosinophilia and systemic symptoms, whose course and prognosis

MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer

Directory of Open Access Journals (Sweden)

George Fountzilas

2009-01-01

Full Text Available Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT. We identified 37 patients treated with this approach, of which 13 (35% achieved a complete response and 10 (27% achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

Science.gov (United States)

Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

2014-10-01

Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Predicting exposure-response associations of ambient particulate matter with mortality in 73 Chinese cities.

Science.gov (United States)

Madaniyazi, Lina; Guo, Yuming; Chen, Renjie; Kan, Haidong; Tong, Shilu

2016-01-01

Estimating the burden of mortality associated with particulates requires knowledge of exposure-response associations. However, the evidence on exposure-response associations is limited in many cities, especially in developing countries. In this study, we predicted associations of particulates smaller than 10 μm in aerodynamic diameter (PM10) with mortality in 73 Chinese cities. The meta-regression model was used to test and quantify which city-specific characteristics contributed significantly to the heterogeneity of PM10-mortality associations for 16 Chinese cities. Then, those city-specific characteristics with statistically significant regression coefficients were treated as independent variables to build multivariate meta-regression models. The model with the best fitness was used to predict PM10-mortality associations in 73 Chinese cities in 2010. Mean temperature, PM10 concentration and green space per capita could best explain the heterogeneity in PM10-mortality associations. Based on city-specific characteristics, we were able to develop multivariate meta-regression models to predict associations between air pollutants and health outcomes reasonably well. Copyright © 2015 Elsevier Ltd. All rights reserved.

The integration of weighted human gene association networks based on link prediction.

Science.gov (United States)

Yang, Jian; Yang, Tinghong; Wu, Duzhi; Lin, Limei; Yang, Fan; Zhao, Jing

2017-01-31

Physical and functional interplays between genes or proteins have important biological meaning for cellular functions. Some efforts have been made to construct weighted gene association meta-networks by integrating multiple biological resources, where the weight indicates the confidence of the interaction. However, it is found that these existing human gene association networks share only quite limited overlapped interactions, suggesting their incompleteness and noise. Here we proposed a workflow to construct a weighted human gene association network using information of six existing networks, including two weighted specific PPI networks and four gene association meta-networks. We applied link prediction algorithm to predict possible missing links of the networks, cross-validation approach to refine each network and finally integrated the refined networks to get the final integrated network. The common information among the refined networks increases notably, suggesting their higher reliability. Our final integrated network owns much more links than most of the original networks, meanwhile its links still keep high functional relevance. Being used as background network in a case study of disease gene prediction, the final integrated network presents good performance, implying its reliability and application significance. Our workflow could be insightful for integrating and refining existing gene association data.

In-home HIV testing and nevirapine dosing by traditional birth attendants in rural Zambia: a feasibility study.

Science.gov (United States)

Brennan, Alana T; Thea, Donald M; Semrau, Katherine; Goggin, Caitlin; Scott, Nancy; Pilingana, Portipher; Botha, Belinda; Mazimba, Arthur; Hamomba, Leoda; Seidenberg, Phil

2014-01-01

Access to lifesaving prevention of mother-to-child transmission (PMTCT) services is problematic in rural Zambia. The simplest intervention used in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is feasible and acceptable by women in rural Zambia. This was a pilot program using TBAs to perform rapid saliva-based HIV testing and administer single-dose NVP in tablet form to the mother at the onset of labor and syrup to the infant after birth. A total of 280 pregnant women were consented and enrolled into the program, of whom 124 (44.3%) gave birth at home with the assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive, and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women tested HIV negative. In the subset of 16 mothers who were HIV positive, 13 (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72 hours after birth, 80% of whom were dosed in the first 24 hours of life. With the substantial shortage of human resources in public health care throughout sub-Saharan Africa, it is extremely valuable to utilize lay health care workers to help extended services beyond the level of the facility. Given the high uptake of PMTCT services we believe that TBAs with proper training and support can successfully provide country-approved PMTCT. © 2013 by the American College of Nurse-Midwives.

Etiology of maculopapular rash in measles and rubella suspected patients from Belarus.

Directory of Open Access Journals (Sweden)

Marina A Yermalovich

Full Text Available As a result of successful implementation of the measles/rubella elimination program, the etiology of more and more double negative cases remains elusive. The present study determined the role of different viruses as causative agents in measles or rubella suspected cases in Belarus. A total of 856 sera sent to the WHO National Laboratory between 2009 and 2011 were tested for specific IgM antibodies to measles virus (MV, rubella virus (RV and human parvovirus B19 (B19V. The negatives were further investigated for antibodies to enterovirus (EV and adenovirus (AdV. Children of up to 3 years were tested for IgM antibodies to human herpesvirus 6 (HHV6. A viral etiology was identified in 451 (52.7% cases, with 6.1% of the samples being positive for MV; 2.6% for RV; 26.2% for B19V; 9.7% for EV; 4.6% for AdV; and 3.6% for HHV6. Almost all measles and rubella cases occurred during limited outbreaks in 2011 and nearly all patients were at least 15 years old. B19V, EV and AdV infections were prevalent both in children and adults and were found throughout the 3 years. B19V occurred mainly in 3-10 years old children and 20-29 years old adults. EV infection was most common in children up to 6 years of age and AdV was confirmed mainly in 3-6 years old children. HHV6 infection was mostly detected in 6-11 months old infants. Laboratory investigation of measles/rubella suspected cases also for B19V, EV, AdV and HHV6 allows diagnosing more than half of all cases, thus strengthening rash/fever disease surveillance in Belarus.

Predictive factors associated with neck pain in patients with cervical disc degeneration

Science.gov (United States)

Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

2017-01-01

Abstract The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease. We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain. In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044–1.112), spondylolisthesis (OR 1.339, 95% CI 1.226–1.462), and annular tear (OR 1.188, 95% CI 1.021–1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022–2.394), spondylolisthesis (OR 1.486, 95% CI 1.082–2.041), and MCs (OR 1.152, 95% CI 1.074–1.234) were associated with PNP. We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain. PMID:29069048

An Unrecognized Rash Progressing to Lyme Carditis: Important Features and Recommendations Regarding Lyme Disease.

Science.gov (United States)

Lee, Shawn; Singla, Montish

2016-01-01

We present a case report of 46-year-old man with no medical history, who complained of extreme fatigue, near-syncope, and palpitations. He initially presented in complete heart block. A transvenous pacemaker was placed in the emergency department, and he was started empirically on Ceftriaxone for Lyme disease. He was admitted and over the course of the next few days, his rhythm regressed to Mobitz type I first-degree atrioventricular block and then to normal sinus rhythm. This case report highlights some important features regarding Lyme carditis, a rare presentation of early disseminated Lyme disease (seen in a few weeks to months after the initial tick bite). In 25%-30% of patients, the characteristic targetoid rash may not be seen, a likely culprit of the disease not being detected early and progressing to disseminated disease. The most common cardiac complaint of Lyme disease is palpitations, occurring in 6.6% of patients, which may not accurately reflect progression into disseminated Lyme disease because it is a nonspecific finding. Conduction abnormality, occurring in 1.8% of patients, is a more specific finding of Borrelia invading cardiac tissue. Finally, this case report highlights a recommendation that patients with confirmed Lyme disease or those presenting with cardiac abnormalities or symptoms who have an atypical profile for a cardiac event should be screened with a 12-lead electrocardiogram, Lyme serology, and be considered for antibiotic therapy with the possibility of temporary pacing.

A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

Science.gov (United States)

Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

2015-12-01

3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Prinitha Pillay

Full Text Available There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI efavirenz (EFV and nevirapine (NVP in first-line antiretroviral therapy (ART.We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2 statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2 = 0% and observational studies (RR 0.65 [0.59-0.71] I(2 = 54%. EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2 = 0% and observational studies (RR 1.06 [1.00-1.12] I(2 = 68%.EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.

Durability of Stavudine, Lamivudine and Nevirapine among Advanced HIV-1 Infected Patients with/without Prior Co-administration of Rifampicin: A 144-week Prospective Study

Directory of Open Access Journals (Sweden)

Prasithisirikul Wisit

2008-10-01

Full Text Available Abstract Background To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings. Methods A prospective cohort study was conducted among 140 antiretroviral-naïve patients who were enrolled to initiate d4T, 3TC and NVP between November 2004 and March 2005. The objectives were to determine immunological and virological responses after 144 weeks of antiretroviral therapy. Seventy patients with tuberculosis also received rifampicin during the early period of antiviral treatment (TB group. Results Of all, median (IQR baseline CD4 cell count was 31 (14–79 cells/mm3; median (IQR baseline HIV-1 RNA was 433,500 (169,000–750,000 copies/mL. The average body weight was 55 kilograms. By intention-to-treat analysis at 144 weeks, the overall percentage of patients who achieved plasma HIV-1 RNA P = 0.731. Eight (5.8% patients discontinued d4T due to neuropathy and/or symptomatic lactic acidosis. Conclusion The overall durability and efficacy of antiviral response of d4T, 3TC and NVP are satisfied and they are not different between HIV-1 infected patients with and without co-administration of rifampicin due to tuberculosis. However, stavudine-related adverse effects are concerns. Trial registration ClinicalTrials.gov Identifier NCT00703898

Predictive Validity of National Basketball Association Draft Combine on Future Performance.

Science.gov (United States)

Teramoto, Masaru; Cross, Chad L; Rieger, Randall H; Maak, Travis G; Willick, Stuart E

2018-02-01

Teramoto, M, Cross, CL, Rieger, RH, Maak, TG, and Willick, SE. Predictive validity of national basketball association draft combine on future performance. J Strength Cond Res 32(2): 396-408, 2018-The National Basketball Association (NBA) Draft Combine is an annual event where prospective players are evaluated in terms of their athletic abilities and basketball skills. Data collected at the Combine should help NBA teams select right the players for the upcoming NBA draft; however, its value for predicting future performance of players has not been examined. This study investigated predictive validity of the NBA Draft Combine on future performance of basketball players. We performed a principal component analysis (PCA) on the 2010-2015 Combine data to reduce correlated variables (N = 234), a correlation analysis on the Combine data and future on-court performance to examine relationships (maximum pairwise N = 217), and a robust principal component regression (PCR) analysis to predict first-year and 3-year on-court performance from the Combine measures (N = 148 and 127, respectively). Three components were identified within the Combine data through PCA (= Combine subscales): length-size, power-quickness, and upper-body strength. As per the correlation analysis, the individual Combine items for anthropometrics, including height without shoes, standing reach, weight, wingspan, and hand length, as well as the Combine subscale of length-size, had positive, medium-to-large-sized correlations (r = 0.313-0.545) with defensive performance quantified by Defensive Box Plus/Minus. The robust PCR analysis showed that the Combine subscale of length-size was a predictor most significantly associated with future on-court performance (p ≤ 0.05), including Win Shares, Box Plus/Minus, and Value Over Replacement Player, followed by upper-body strength. In conclusion, the NBA Draft Combine has value for predicting future performance of players.

Preventive effect of kampo medicine (hangeshashin-to, TJ-14 plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Ichiki M

2017-10-01

Full Text Available Masao Ichiki,1 Hiroshi Wataya,2 Kazuhiko Yamada,3 Nobuko Tsuruta,4 Hiroaki Takeoka,1 Yusuke Okayama,1 Jun Sasaki,1 Tomoaki Hoshino3 1Department of Respiratory Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, 2Division of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka City, 3Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University, Kurume City, 4Department of Respiratory Medicine, Hamanomachi Hospital, Fukuoka City, Fukuoka, Japan Purpose: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14 might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash.Patients and methods: First- and second-generation epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day and minocycline (100 mg/day were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3 diarrhea (increase of ≥7 stools/day over baseline during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake and ≥ G3 skin toxicity (severe or medically significant but not immediately life-threatening.Results: A total of 29 patients (nine men and 20 women; median age, 66�

Pityriasis Rosea: A rash that should be recognized by the primary care physician. Study of 30 cases

Directory of Open Access Journals (Sweden)

Igor López-Carrera

2014-08-01

Full Text Available Background: Pityriasis rosea is an acute disseminated rash of unknown etiology and prolonged duration, characterized by erythematous- squamous plaques. Despite having an ostentatious clinical picture for both the patient and family, it is self-limited and usually resolves without sequelae. Pityriasis rosea is often erroneously diagnosed as mycosis and given unnecessary treatment. Objective: To describe the clinical and demographical features of pity- riasis rosea in a group of Mexican pediatric patients. Patients and methods: Retrospective and descriptive study in which the clinical and demographic features of patients attended at the department of dermatology of the National Institute of Pediatrics with diagnosis of pityriasis rosea within a ten year period were analysed. Results: Thirty patients with pityriasis rosea, with a frequency of 3.6 per 1000 dermatological patients. Pityriasis rosea was more frequent in females with a ratio of 1.5 to 1 and a mean age of 10 years. More than half of the patients (56% had an atypical presentation, and biopsy was mandatory in 7 patients to establish the final diagnosis. Conclusions: The knowledge of the clinical features of pityriasis rosea by primary care physicians will prevent from unnecessary work-up and treatments.

Left ventricular mass in HIV-infected patients.

Science.gov (United States)

Olalla, J; Pombo, M; Del Arco, A; de la Torre, J; Urdiales, D; García-Alegría, J

2013-01-01

The HIV infection has been associated with an increased incidence of vascular events. Left ventricular mass (LVM) is independently associated with greater overall mortality. Various studies have shown that patients with HIV infection have higher LVM than the uninfected population. We aim to describe the distribution of LVM in an extensive series of patients with HIV infection, and the factors associated with its increase. A cross-sectional study was performed in HIV-infected patients followed in our center from 1 December 2009 to 28 February 2011. A transthoracic echocardiography (TTE) was performed in all patients who gave their consent. Demographic variables, viroimmunological status, cardiovascular risk factors, vascular risk at 10 years (VR10) and history of exposure to antiretroviral drugs were collected. LVM was considered to be the quantitative dependent variable. A univariate analysis was performed, including in the multivariate analysis those variables with P<,05. A TTE was performed in 400 patients, and the LVM was calculated in 388. Mean age was 45 years, 75.5 males. Mean LVM was 39.54g/m(2.7)(95% CI: 38.35-40.73). Age, height, body mass index, VR10, hypertension, dyslipidemia, different medications within the cardiovascular area and having taken nevirapine have been used in the history of the patient were associated to greater LVM. In the multivariate analysis, use of nevirapine in the history of the patient and VR10 remained in the model. VR10 may be associated with greater LVM. The relationship with nevirapine may respond to an indication bias. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Mini-review: Prediction errors, attention and associative learning.

Science.gov (United States)

Holland, Peter C; Schiffino, Felipe L

2016-05-01

Most modern theories of associative learning emphasize a critical role for prediction error (PE, the difference between received and expected events). One class of theories, exemplified by the Rescorla-Wagner (1972) model, asserts that PE determines the effectiveness of the reinforcer or unconditioned stimulus (US): surprising reinforcers are more effective than expected ones. A second class, represented by the Pearce-Hall (1980) model, argues that PE determines the associability of conditioned stimuli (CSs), the rate at which they may enter into new learning: the surprising delivery or omission of a reinforcer enhances subsequent processing of the CSs that were present when PE was induced. In this mini-review we describe evidence, mostly from our laboratory, for PE-induced changes in the associability of both CSs and USs, and the brain systems involved in the coding, storage and retrieval of these altered associability values. This evidence favors a number of modifications to behavioral models of how PE influences event processing, and suggests the involvement of widespread brain systems in animals' responses to PE. Copyright © 2016 Elsevier Inc. All rights reserved.

Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells.

Directory of Open Access Journals (Sweden)

Markus Hecht

Full Text Available Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo.Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50 were calculated and compared to the blood levels in our patients and published data.The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5 μmol/l (= 9944 ng/ml, Nevirapine 239 μmol/l (= 63,786 ng/ml, Etravirine 89.0 μmol/l (= 38,740 ng/ml, Lersivirine 543 μmol/l (= 168,523 ng/ml, Delavirdine 171 μmol/l (= 78,072 ng/ml, Rilpivirine 24.4 μmol/l (= 8941 ng/ml. As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587 ng/ml (range 162-15,363 ng/ml, of Rilpivirine 144 ng/ml (range 0-572 ng/ml and of Nevirapine 4955 ng/ml (range 1856-8697 ng/ml. Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients.All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic

iPat: intelligent prediction and association tool for genomic research.

Science.gov (United States)

Chen, Chunpeng James; Zhang, Zhiwu

2018-06-01

The ultimate goal of genomic research is to effectively predict phenotypes from genotypes so that medical management can improve human health and molecular breeding can increase agricultural production. Genomic prediction or selection (GS) plays a complementary role to genome-wide association studies (GWAS), which is the primary method to identify genes underlying phenotypes. Unfortunately, most computing tools cannot perform data analyses for both GWAS and GS. Furthermore, the majority of these tools are executed through a command-line interface (CLI), which requires programming skills. Non-programmers struggle to use them efficiently because of the steep learning curves and zero tolerance for data formats and mistakes when inputting keywords and parameters. To address these problems, this study developed a software package, named the Intelligent Prediction and Association Tool (iPat), with a user-friendly graphical user interface. With iPat, GWAS or GS can be performed using a pointing device to simply drag and/or click on graphical elements to specify input data files, choose input parameters and select analytical models. Models available to users include those implemented in third party CLI packages such as GAPIT, PLINK, FarmCPU, BLINK, rrBLUP and BGLR. Users can choose any data format and conduct analyses with any of these packages. File conversions are automatically conducted for specified input data and selected packages. A GWAS-assisted genomic prediction method was implemented to perform genomic prediction using any GWAS method such as FarmCPU. iPat was written in Java for adaptation to multiple operating systems including Windows, Mac and Linux. The iPat executable file, user manual, tutorials and example datasets are freely available at http://zzlab.net/iPat. zhiwu.zhang@wsu.edu.

Encephalitis associated with inappropriate antidiuretic hormone secretion due to chikungunya infection in Recife, State of Pernambuco, Brazil

Directory of Open Access Journals (Sweden)

Norma Lucena-Silva

Full Text Available Abstract The symptoms of chikungunya virus (CHIKV infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.

Prediction of disease and phenotype associations from genome-wide association studies.

Directory of Open Access Journals (Sweden)

Stephanie N Lewis

Full Text Available Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases.Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

Factors associated to cases of Brazilian Spotted Fever, Minas Gerais, 1995- 2002

Directory of Open Access Journals (Sweden)

Simone Berger Calic

2015-10-01

Full Text Available ABSTRACT. Calic S.B., Rocha C.M.B.M, Bruhn F.R.P., Barros R.A. & Leite R.C. [Factors associated to cases of Brazilian Spotted Fever, Minas Gerais, 1995- 2002.] Fatores associados aos casos de Febre Maculosa Brasileira frente aos suspeitos não confirmados, Minas Gerais, 1995 a 2002. Revista Brasileira de Medicina Veterinária, 37(3:239-244, 2015. Instituto Otávio Magalhães, Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Gameleira, Belo Horizonte, MG 30510- 010, Brasil. E-mail: sbcalic@gmail.com The aim of this study was to evaluate factors and symptoms associated with confirmed cases of FMB in Minas Gerais. For this, was conducted a retrospective study using epidemiological records received by the Central Laboratory (LACEN of MG in the period 1995-2002. Cases were suspected patients after clinical and epidemiological assessment for BSF and seropositive for Rickettsia ricketsii (IFAT 1:64 in at least one serum sample. As negative suspects were those that have no seroconversion in two consecutive samples to BSF. After adjustment of multiple logistic regression analysis, only the occurrence of rash and seizures were associated with symptoms FMB. Using analysis of main components symptoms that characterized the cases were: rash, convulsions and coma. Moreover cases have a high relation with hospitalization and lack of similar cases. The FMB in Minas Gerais is a serious disease and need early diagnosis.

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

Directory of Open Access Journals (Sweden)

Siripassorn Krittaecho

2013-01-01

Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

A Meta-Path-Based Prediction Method for Human miRNA-Target Association

Directory of Open Access Journals (Sweden)

Jiawei Luo

2016-01-01

Full Text Available MicroRNAs (miRNAs are short noncoding RNAs that play important roles in regulating gene expressing, and the perturbed miRNAs are often associated with development and tumorigenesis as they have effects on their target mRNA. Predicting potential miRNA-target associations from multiple types of genomic data is a considerable problem in the bioinformatics research. However, most of the existing methods did not fully use the experimentally validated miRNA-mRNA interactions. Here, we developed RMLM and RMLMSe to predict the relationship between miRNAs and their targets. RMLM and RMLMSe are global approaches as they can reconstruct the missing associations for all the miRNA-target simultaneously and RMLMSe demonstrates that the integration of sequence information can improve the performance of RMLM. In RMLM, we use RM measure to evaluate different relatedness between miRNA and its target based on different meta-paths; logistic regression and MLE method are employed to estimate the weight of different meta-paths. In RMLMSe, sequence information is utilized to improve the performance of RMLM. Here, we carry on fivefold cross validation and pathway enrichment analysis to prove the performance of our methods. The fivefold experiments show that our methods have higher AUC scores compared with other methods and the integration of sequence information can improve the performance of miRNA-target association prediction.

Chinese SLE Treatment and Research Group Registry: III. Association of Autoantibodies with Clinical Manifestations in Chinese Patients with Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Jing Li

2014-01-01

Full Text Available We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P<0.05 associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH; between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05. Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05. Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

Measured and Predicted Variations in Fast Neutron Spectrum in Massive Shields of Water and Concrete

Energy Technology Data Exchange (ETDEWEB)

Aalto, E; Sandlin, R; Fraeki, R

1965-09-15

The absolute magnitude, and the variations in form, of the fast neutron spectrum during deep penetration (0.8 - 1.1 metre) in massive shields of water, ordinary and magnetite concrete have been studied by using threshold detectors (In (n, h'), S(n,p), Al(n, {alpha})). The results have been compared with predictions by two rigorous (NIOBE, Moments method) and two non-rigorous (multigroup removal-diffusion) shielding codes (NRN, RASH D). The absolute results predicted were in general within 50% of the measured ones, i. e. showed as good or better accuracy than thermal and epithermal flux predictions in the same small-reactor configurations. No difference in accuracy was found between the rigorous and non-rigorous methods. The changes in the relative form of the spectrum (indicated by variations in the (Al/S) and (In/S) reaction rate ratios and amounting to factors up to 3 - 4 during a one metre penetration in water) were rather accurately (within 10 - 30%) predicted by all of the methods. The photonuclear excitation of the 335 keV level used for detecting the In(n, n') reaction was found to distort completely the In results in water at penetrations > 50 cm.

Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

Science.gov (United States)

Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

2008-07-10

Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

MKRMDA: multiple kernel learning-based Kronecker regularized least squares for MiRNA-disease association prediction.

Science.gov (United States)

Chen, Xing; Niu, Ya-Wei; Wang, Guang-Hui; Yan, Gui-Ying

2017-12-12

Recently, as the research of microRNA (miRNA) continues, there are plenty of experimental evidences indicating that miRNA could be associated with various human complex diseases development and progression. Hence, it is necessary and urgent to pay more attentions to the relevant study of predicting diseases associated miRNAs, which may be helpful for effective prevention, diagnosis and treatment of human diseases. Especially, constructing computational methods to predict potential miRNA-disease associations is worthy of more studies because of the feasibility and effectivity. In this work, we developed a novel computational model of multiple kernels learning-based Kronecker regularized least squares for MiRNA-disease association prediction (MKRMDA), which could reveal potential miRNA-disease associations by automatically optimizing the combination of multiple kernels for disease and miRNA. MKRMDA obtained AUCs of 0.9040 and 0.8446 in global and local leave-one-out cross validation, respectively. Meanwhile, MKRMDA achieved average AUCs of 0.8894 ± 0.0015 in fivefold cross validation. Furthermore, we conducted three different kinds of case studies on some important human cancers for further performance evaluation. In the case studies of colonic cancer, esophageal cancer and lymphoma based on known miRNA-disease associations in HMDDv2.0 database, 76, 94 and 88% of the corresponding top 50 predicted miRNAs were confirmed by experimental reports, respectively. In another two kinds of case studies for new diseases without any known associated miRNAs and diseases only with known associations in HMDDv1.0 database, the verified ratios of two different cancers were 88 and 94%, respectively. All the results mentioned above adequately showed the reliable prediction ability of MKRMDA. We anticipated that MKRMDA could serve to facilitate further developments in the field and the follow-up investigations by biomedical researchers.

Different patterns of skin manifestations associated with parvovirus B19 primary infection in adults.

Science.gov (United States)

Mage, Valentia; Lipsker, Dan; Barbarot, Sébastien; Bessis, Didier; Chosidow, Olivier; Del Giudice, Pascal; Aractingi, Sélim; Avouac, Jérôme; Bernier, Claire; Descamps, Vincent; Dupin, Nicolas

2014-07-01

Skin involvement is reported during primary parvovirus B19 infection in adults. We sought to describe the cutaneous presentations associated with parvovirus B19 primary infection in adults. We conducted a descriptive, retrospective, multicenter study. The patients included (>18 years old) had well-established primary infections with parvovirus B19. Twenty-nine patients were identified between 1992 and 2013 (17 women, 12 men). The elementary dermatologic lesions were mostly erythematous (86%) and often purpuric (69%). Pruritus was reported in 48% of cases. The rash predominated on the legs (93%), trunk (55%), and arms (45%), with a lower frequency of facial involvement (20%). Four different but sometimes overlapping patterns were identified (45%): exanthema, which was reticulated and annular in some cases (80%); the gloves-and-socks pattern (24%); the periflexural pattern (28%); and palpable purpura (24%). The limitations of this study were its retrospective design and possible recruitment bias in tertiary care centers. Our findings suggest that primary parvovirus B19 infection is associated with polymorphous skin manifestations with 4 predominant, sometimes overlapping, patterns. The acral or periflexural distribution of the rash and the presence of purpuric or annular/reticulate lesions are highly suggestive of parvovirus B19 infection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

SRMDAP: SimRank and Density-Based Clustering Recommender Model for miRNA-Disease Association Prediction

Directory of Open Access Journals (Sweden)

Xiaoying Li

2018-01-01

Full Text Available Aberrant expression of microRNAs (miRNAs can be applied for the diagnosis, prognosis, and treatment of human diseases. Identifying the relationship between miRNA and human disease is important to further investigate the pathogenesis of human diseases. However, experimental identification of the associations between diseases and miRNAs is time-consuming and expensive. Computational methods are efficient approaches to determine the potential associations between diseases and miRNAs. This paper presents a new computational method based on the SimRank and density-based clustering recommender model for miRNA-disease associations prediction (SRMDAP. The AUC of 0.8838 based on leave-one-out cross-validation and case studies suggested the excellent performance of the SRMDAP in predicting miRNA-disease associations. SRMDAP could also predict diseases without any related miRNAs and miRNAs without any related diseases.

Analyzing and Predicting Effort Associated with Finding and Fixing Software Faults

Science.gov (United States)

Hamill, Maggie; Goseva-Popstojanova, Katerina

2016-01-01

Context: Software developers spend a significant amount of time fixing faults. However, not many papers have addressed the actual effort needed to fix software faults. Objective: The objective of this paper is twofold: (1) analysis of the effort needed to fix software faults and how it was affected by several factors and (2) prediction of the level of fix implementation effort based on the information provided in software change requests. Method: The work is based on data related to 1200 failures, extracted from the change tracking system of a large NASA mission. The analysis includes descriptive and inferential statistics. Predictions are made using three supervised machine learning algorithms and three sampling techniques aimed at addressing the imbalanced data problem. Results: Our results show that (1) 83% of the total fix implementation effort was associated with only 20% of failures. (2) Both safety critical failures and post-release failures required three times more effort to fix compared to non-critical and pre-release counterparts, respectively. (3) Failures with fixes spread across multiple components or across multiple types of software artifacts required more effort. The spread across artifacts was more costly than spread across components. (4) Surprisingly, some types of faults associated with later life-cycle activities did not require significant effort. (5) The level of fix implementation effort was predicted with 73% overall accuracy using the original, imbalanced data. Using oversampling techniques improved the overall accuracy up to 77%. More importantly, oversampling significantly improved the prediction of the high level effort, from 31% to around 85%. Conclusions: This paper shows the importance of tying software failures to changes made to fix all associated faults, in one or more software components and/or in one or more software artifacts, and the benefit of studying how the spread of faults and other factors affect the fix implementation

Predictive Factors associated with Death of Elderly in Nursing Homes

Directory of Open Access Journals (Sweden)

Kiwol Sung, PhD, RN

2014-06-01

Conclusion: Dyspnea, problematic behaviors, and ADL data were identified as the key factors associated with death among nursing home residents. Future plans for the prediction of death among nursing home residents can be made by nursing staff, factoring in these identified variables, to ensure more comfortable conditions and more responsive care.

Test-Retest Reliability and Predictive Validity of the Implicit Association Test in Children

Science.gov (United States)

Rae, James R.; Olson, Kristina R.

2018-01-01

The Implicit Association Test (IAT) is increasingly used in developmental research despite minimal evidence of whether children's IAT scores are reliable across time or predictive of behavior. When test-retest reliability and predictive validity have been assessed, the results have been mixed, and because these studies have differed on many…

Matrix factorization-based data fusion for the prediction of lncRNA-disease associations.

Science.gov (United States)

Fu, Guangyuan; Wang, Jun; Domeniconi, Carlotta; Yu, Guoxian

2018-05-01

Long non-coding RNAs (lncRNAs) play crucial roles in complex disease diagnosis, prognosis, prevention and treatment, but only a small portion of lncRNA-disease associations have been experimentally verified. Various computational models have been proposed to identify lncRNA-disease associations by integrating heterogeneous data sources. However, existing models generally ignore the intrinsic structure of data sources or treat them as equally relevant, while they may not be. To accurately identify lncRNA-disease associations, we propose a Matrix Factorization based LncRNA-Disease Association prediction model (MFLDA in short). MFLDA decomposes data matrices of heterogeneous data sources into low-rank matrices via matrix tri-factorization to explore and exploit their intrinsic and shared structure. MFLDA can select and integrate the data sources by assigning different weights to them. An iterative solution is further introduced to simultaneously optimize the weights and low-rank matrices. Next, MFLDA uses the optimized low-rank matrices to reconstruct the lncRNA-disease association matrix and thus to identify potential associations. In 5-fold cross validation experiments to identify verified lncRNA-disease associations, MFLDA achieves an area under the receiver operating characteristic curve (AUC) of 0.7408, at least 3% higher than those given by state-of-the-art data fusion based computational models. An empirical study on identifying masked lncRNA-disease associations again shows that MFLDA can identify potential associations more accurately than competing models. A case study on identifying lncRNAs associated with breast, lung and stomach cancers show that 38 out of 45 (84%) associations predicted by MFLDA are supported by recent biomedical literature and further proves the capability of MFLDA in identifying novel lncRNA-disease associations. MFLDA is a general data fusion framework, and as such it can be adopted to predict associations between other biological

Early-Onset Chronic Inflammatory Disease Associated with Maternal Microchimerism

Directory of Open Access Journals (Sweden)

Tomoaki Ishikawa

2012-01-01

Full Text Available Maternal microchimerism (mMc refers to the presence of a small population of cells originating from the mother. Whether mMc leads to autoimmune responses in children remains controversial. We describe here an 11-year-old boy with persistent fever and elevated levels of C-reactive protein from infancy onward. During infancy, the patient presented with high fever, skin rashes, and hepatic dysfunction. Careful examination including a liver biopsy failed to reveal the cause. At 4 years old, petechiae developed associated with thrombocytopenia and positive anti-dsDNA autoantibodies. Steroid pulse therapy was effective, but the effect of low-dose prednisone was insufficient. At age 9, an extensive differential diagnosis was considered especially for infantile onset autoinflammatory disorders but failed to make a definitive diagnosis. On admission, the patient exhibited short stature, hepatosplenomegaly, generalized superficial lymphadenopathy, and rashes. Laboratory findings revealed anemia, elevated levels of inflammation markers, and hypergammaglobulinemia. Serum complement levels were normal. Serum levels of IL-6 and B-cell activating factor were elevated. Viral infections were not identified. Although HLA typing revealed no noninherited maternal antigens in lymphocytes, female cells were demonstrated in the patient’s skin and lymph nodes, suggesting that maternal microchimerism might be involved in the pathogenesis of fever without source in infants.

Performance of predictive models in phase equilibria of complex associating systems: PC-SAFT and CEOS/GE

Directory of Open Access Journals (Sweden)

N. Bender

2013-03-01

Full Text Available Cubic equations of state combined with excess Gibbs energy predictive models (like UNIFAC and equations of state based on applied statistical mechanics are among the main alternatives for phase equilibria prediction involving polar substances in wide temperature and pressure ranges. In this work, the predictive performances of the PC-SAFT with association contribution and Peng-Robinson (PR combined with UNIFAC (Do through mixing rules are compared. Binary and multi-component systems involving polar and non-polar substances were analyzed. Results were also compared to experimental data available in the literature. Results show a similar predictive performance for PC-SAFT with association and cubic equations combined with UNIFAC (Do through mixing rules. Although PC-SAFT with association requires less parameters, it is more complex and requires more computation time.

Predictability of Mobile Phone Associations

DEFF Research Database (Denmark)

Jensen, Bjørn Sand; Larsen, Jan; Hansen, Lars Kai

2010-01-01

Prediction and understanding of human behavior is of high importance in many modern applications and research areas ranging from context-aware services, wireless resource allocation to social sciences. In this study we collect a novel dataset using standard mobile phones and analyze how the predi...... representation, and general behavior. This is of vital interest in the development of context-aware services which rely on forecasting based on mobile phone sensors.......Prediction and understanding of human behavior is of high importance in many modern applications and research areas ranging from context-aware services, wireless resource allocation to social sciences. In this study we collect a novel dataset using standard mobile phones and analyze how...... the predictability of mobile sensors, acting as proxies for humans, change with time scale and sensor type such as GSM and WLAN. Applying recent information theoretic methods, it is demonstrated that an upper bound on predictability is relatively high for all sensors given the complete history (typically above 90...

Factors associated with therapeutic inertia in hypertension: validation of a predictive model.

Science.gov (United States)

Redón, Josep; Coca, Antonio; Lázaro, Pablo; Aguilar, Ma Dolores; Cabañas, Mercedes; Gil, Natividad; Sánchez-Zamorano, Miguel Angel; Aranda, Pedro

2010-08-01

To study factors associated with therapeutic inertia in treating hypertension and to develop a predictive model to estimate the probability of therapeutic inertia in a given medical consultation, based on variables related to the consultation, patient, physician, clinical characteristics, and level of care. National, multicentre, observational, cross-sectional study in primary care and specialist (hospital) physicians who each completed a questionnaire on therapeutic inertia, provided professional data and collected clinical data on four patients. Therapeutic inertia was defined as a consultation in which treatment change was indicated (i.e., SBP >or= 140 or DBP >or= 90 mmHg in all patients; SBP >or= 130 or DBP >or= 80 in patients with diabetes or stroke), but did not occur. A predictive model was constructed and validated according to the factors associated with therapeutic inertia. Data were collected on 2595 patients and 13,792 visits. Therapeutic inertia occurred in 7546 (75%) of the 10,041 consultations in which treatment change was indicated. Factors associated with therapeutic inertia were primary care setting, male sex, older age, SPB and/or DBP values close to normal, treatment with more than one antihypertensive drug, treatment with an ARB II, and more than six visits/year. Physician characteristics did not weigh heavily in the association. The predictive model was valid internally and externally, with acceptable calibration, discrimination and reproducibility, and explained one-third of the variability in therapeutic inertia. Although therapeutic inertia is frequent in the management of hypertension, the factors explaining it are not completely clear. Whereas some aspects of the consultations were associated with therapeutic inertia, physician characteristics were not a decisive factor.

Evaluation of the predictive capacity of DNA variants associated with straight hair in Europeans.

Science.gov (United States)

Pośpiech, Ewelina; Karłowska-Pik, Joanna; Marcińska, Magdalena; Abidi, Sarah; Andersen, Jeppe Dyrberg; Berge, Margreet van den; Carracedo, Ángel; Eduardoff, Mayra; Freire-Aradas, Ana; Morling, Niels; Sijen, Titia; Skowron, Małgorzata; Söchtig, Jens; Syndercombe-Court, Denise; Weiler, Natalie; Schneider, Peter M; Ballard, David; Børsting, Claus; Parson, Walther; Phillips, Chris; Branicki, Wojciech

2015-11-01

DNA-based prediction of hair morphology, defined as straight, curly or wavy hair, could contribute to an improved description of an unknown offender and allow more accurate forensic reconstructions of physical appearance in the field of forensic DNA phenotyping. Differences in scalp hair morphology are significant at the worldwide scale and within Europe. The only genome-wide association study made to date revealed the Trichohyalin gene (TCHH) to be significantly associated with hair morphology in Europeans and reported weaker associations for WNT10A and FRAS1 genes. We conducted a study that centered on six SNPs located in these three genes with a sample of 528 individuals from Poland. The predictive capacity of the candidate DNA variants was evaluated using logistic regression; classification and regression trees; and neural networks, by applying a 10-fold cross validation procedure. Additionally, an independent test set of 142 males from six European populations was used to verify performance of the developed prediction models. Our study confirmed association of rs11803731 (TCHH), rs7349332 (WNT10A) and rs1268789 (FRAS1) SNPs with hair morphology. The combined genotype risk score for straight hair had an odds ratio of 2.7 and these predictors explained ∼ 8.2% of the total variance. The selected three SNPs were found to predict straight hair with a high sensitivity but low specificity when a 10-fold cross validation procedure was applied and the best results were obtained using the neural networks approach (AUC=0.688, sensitivity=91.2%, specificity=23.0%). Application of the neural networks model with 65% probability threshold on an additional test set gave high sensitivity (81.4%) and improved specificity (50.0%) with a total of 78.7% correct calls, but a high non-classification rate (66.9%). The combined TTGGGG SNP genotype for rs11803731, rs7349332, rs1268789 (European frequency=4.5%) of all six straight hair-associated alleles was identified as the best

Prediction of Associations between OMIM Diseases and MicroRNAs by Random Walk on OMIM Disease Similarity Network

Directory of Open Access Journals (Sweden)

Hailin Chen

2013-01-01

Full Text Available Increasing evidence has revealed that microRNAs (miRNAs play important roles in the development and progression of human diseases. However, efforts made to uncover OMIM disease-miRNA associations are lacking and the majority of diseases in the OMIM database are not associated with any miRNA. Therefore, there is a strong incentive to develop computational methods to detect potential OMIM disease-miRNA associations. In this paper, random walk on OMIM disease similarity network is applied to predict potential OMIM disease-miRNA associations under the assumption that functionally related miRNAs are often associated with phenotypically similar diseases. Our method makes full use of global disease similarity values. We tested our method on 1226 known OMIM disease-miRNA associations in the framework of leave-one-out cross-validation and achieved an area under the ROC curve of 71.42%. Excellent performance enables us to predict a number of new potential OMIM disease-miRNA associations and the newly predicted associations are publicly released to facilitate future studies. Some predicted associations with high ranks were manually checked and were confirmed from the publicly available databases, which was a strong evidence for the practical relevance of our method.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

Science.gov (United States)

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Brief implicit association test: Validity and utility in prediction of voting behavior

Directory of Open Access Journals (Sweden)

Pavlović Maša D.

2013-01-01

Full Text Available We employed the Brief Implicit Association Test (a recently developed short version of IAT to measure implicit political attitudes toward four political parties running for Serbian parliament. To test its criterion validity, we measured voting intention and actual voting behavior. In addition, we introduced political involvement as a potential moderator of the BIAT’s predictive and incremental validity. The BIAT demonstrated good internal and predictive validity, but lacked incremental validity over self-report measures. Predictive power of the BIAT was moderated by political involvement - the BIAT scores were stronger predictors of voting intention and behavior among voters highly involved in politics. [Projekat Ministarstva nauke Republike Srbije, br. 179018

Impact of adverse events of antiretroviral treatment on regimen change and mortality in Ugandan children

Directory of Open Access Journals (Sweden)

Ntambwe Malangu

2010-06-01

Objectives: The purpose of this study was to determine the prevalence of the adverse events of antiretroviral treatment, their impact on mortality and the change in regimens prescribed to children treated at Mildway Centre in Uganda. Method: A retrospective chart review was performed for children younger than 6 years, treated since the Mildway Centre was opened in 1999. In order to achieve a larger sample, the records of children treated from January 2000 to July 2005 were included in the study. A pre-tested data collection form was used to collate socio-demographic and clinical data of the patients. These included the documented adverse events, causes of death, stage of infection, duration of treatment, regimen prescribed, year of enrolment into the treatment program, as well as whether or not they were still alive. Descriptive statistics were used in the analysis of data. Results: Of the 179 children, the majority were males and had a median age of 4 years. The majority (58.8% of children had suffered from severe immune depression since they met the WHO clinical stage III and IV, 73.8% had a baseline CD4T of less than 15%. Four regimens were prescribed to the children. The most common was a regimen containing zidovudine, lamivudine, and nevirapine (34.6%, followed by a regimen containing stavudine, lamivudine, and nevirapine (27.9%. Eleven children (6.1% had their regimen changed, of which six (54.5% were due to adverse events. The prevalence of adverse events was 8%; of the 14 documented adverse events, the most common were severe anaemia (3, vomiting (3, and skin rashes (3. After 12 months on treatment, 8% of the patients had died. The most common causes of death were infectious diseases (28.6%, severe anaemia (21.4%, and severe dehydration (21.4%. Conclusion: The prevalence of adverse events was 8%; they were responsible for 54.5% of regimen changes and 21.4% of deaths in children treated at the study site. These findings suggest the need for incorporating

[Cryopyrine-associated periodic syndrome: CAPS seen from adulthood].

Science.gov (United States)

Koné-Paut, I

2015-04-01

Cryopyrin-associated periodic syndrome is a rare hereditary periodic fever syndrome for which, the genetic mechanism, mutation in the NLRP3 gene, has allowed to gather 3 clinical phenotypes (familial cold urticaria [FCAS], Muckle-Wells syndrome [MWS], and chronic infantile neurological cutaneous and articular syndrome [CINCA]) initially described independently, and to discover the NLRP3 inflammasome, a key receptor of the innate immunity, which regulates the interleukine-1β secretion into the mononuclear cells. The clinical manifestation of CAPS : urticaria-like skin rash, eyes redness, myalgia and sensory deafness are not specific, if considered separately, and that often leads to a wandering diagnosis through a complex medical journey including various specialists. The diagnostic delay is deleterious to patients compromising their quality of life and exposing them to neurosensory complications and renal failure by secondary amyloidosis. The paediatric onset of disease, the family history, the trigger of symptoms by the cold, and the recognition of the skin rash as neutrophilic are important clues before diagnostic confirmation by genetic testing. Interleukine-1 blockade is the only effective treatment of CAPS symptoms which often may stabilize (rarely regression) the sensory involvement and in some cases may allow the regression of secondary amyloidosis. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Prediction of Associations between microRNAs and Gene Expression in Glioma Biology.

Directory of Open Access Journals (Sweden)

Stefan Wuchty

Full Text Available Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells.

Genomic Prediction and Association Mapping of Curd-Related Traits in Gene Bank Accessions of Cauliflower.

Science.gov (United States)

Thorwarth, Patrick; Yousef, Eltohamy A A; Schmid, Karl J

2018-02-02

Genetic resources are an important source of genetic variation for plant breeding. Genome-wide association studies (GWAS) and genomic prediction greatly facilitate the analysis and utilization of useful genetic diversity for improving complex phenotypic traits in crop plants. We explored the potential of GWAS and genomic prediction for improving curd-related traits in cauliflower ( Brassica oleracea var. botrytis ) by combining 174 randomly selected cauliflower gene bank accessions from two different gene banks. The collection was genotyped with genotyping-by-sequencing (GBS) and phenotyped for six curd-related traits at two locations and three growing seasons. A GWAS analysis based on 120,693 single-nucleotide polymorphisms identified a total of 24 significant associations for curd-related traits. The potential for genomic prediction was assessed with a genomic best linear unbiased prediction model and BayesB. Prediction abilities ranged from 0.10 to 0.66 for different traits and did not differ between prediction methods. Imputation of missing genotypes only slightly improved prediction ability. Our results demonstrate that GWAS and genomic prediction in combination with GBS and phenotyping of highly heritable traits can be used to identify useful quantitative trait loci and genotypes among genetically diverse gene bank material for subsequent utilization as genetic resources in cauliflower breeding. Copyright © 2018 Thorwarth et al.

Genomic Prediction and Association Mapping of Curd-Related Traits in Gene Bank Accessions of Cauliflower

Directory of Open Access Journals (Sweden)

Patrick Thorwarth

2018-02-01

Full Text Available Genetic resources are an important source of genetic variation for plant breeding. Genome-wide association studies (GWAS and genomic prediction greatly facilitate the analysis and utilization of useful genetic diversity for improving complex phenotypic traits in crop plants. We explored the potential of GWAS and genomic prediction for improving curd-related traits in cauliflower (Brassica oleracea var. botrytis by combining 174 randomly selected cauliflower gene bank accessions from two different gene banks. The collection was genotyped with genotyping-by-sequencing (GBS and phenotyped for six curd-related traits at two locations and three growing seasons. A GWAS analysis based on 120,693 single-nucleotide polymorphisms identified a total of 24 significant associations for curd-related traits. The potential for genomic prediction was assessed with a genomic best linear unbiased prediction model and BayesB. Prediction abilities ranged from 0.10 to 0.66 for different traits and did not differ between prediction methods. Imputation of missing genotypes only slightly improved prediction ability. Our results demonstrate that GWAS and genomic prediction in combination with GBS and phenotyping of highly heritable traits can be used to identify useful quantitative trait loci and genotypes among genetically diverse gene bank material for subsequent utilization as genetic resources in cauliflower breeding.

Pediatric Viral Exanthema: A Review Article

Directory of Open Access Journals (Sweden)

Mohammed Jafar Saffar

2017-04-01

Full Text Available Context Many diseases caused by viral agents are associated with fever and cutaneous manifestations. Viral exanthema is a widespread nonspecific skin rash, commonly characterized by generalized eruption of erythematous macules and papular lesions. Although these rashes are mostly benign and self-limited, some may be serious and life-threatening. Differentiation between severe and benign types is clinically important and life-saving. Evidence Acquisition In this narrative review, electronic databases, including Google Scholar, Science Direct, PubMed (including Medline, Web of Science, Scientific Information Database, and Scopus, were searched. We conducted a narrative review of papers published on pediatric viral exanthema during 2000 - 2016. The used keywords included “viral exanthema”, “fever”, and “skin rash”. Articles on skin rash, caused by drug reactions or nonviral exanthema, were excluded. Results Different viral agents can cause different types of skin reactions. Cutaneous manifestations and skin rashes can be categorized, based on the form of the rash (macular, papular, vesicular, blistery, petechial, and purpuric or the general term, which denotes illnesses such as measles-like morbilliform rash, rubella or rubelliform rash, and scarlatiniform rash, a scarlet-fever like infection. Conclusions Based on the findings, a systematic approach relying on accurate history-taking and analysis of epidemiological cues and rash characteristics is of great significance.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS: 11 years retrospective study in Thailand

Directory of Open Access Journals (Sweden)

Akarin Hiransuthikul

2016-10-01

Conclusions: DRESS is associated with severe morbidity and mortality. Phenytoin, nevirapine, allopurinol, and cotrimoxazole were the major causes. Allopurinol-induced DRESS had the longest onset time, and was associated with higher eosinophilia and incidence of renal involvement. Raising awareness among both health care providers and public for early detection and withdrawal of the causative agent is critical to save life and reduce morbidity.

Herpes zoster-associated voiding dysfunction in hematopoietic malignancy patients.

Science.gov (United States)

Imafuku, Shinichi; Takahara, Masakazu; Uenotsuchi, Takeshi; Iwato, Koji; Furue, Masutaka

2008-01-01

Voiding dysfunction is a rare but important complication of lumbo-sacral herpes zoster. Although the symptoms are transient, the clinical impact on immunocompromised patients cannot be overlooked. To clarify the time course of voiding dysfunction in herpes zoster, 13 herpes zoster patients with voiding dysfunction were retrospectively analyzed. Of 13 patients, 12 had background disease, and six of these were hematopoietic malignancies; four of these patients were hematopoietic stem cell transplant (HSCT) recipients. Ten patients had sacral lesions, two had lumbar, and one had thoracic lesions. Interestingly, patients with severe rash, or with hematopoietic malignancy had later onset of urinary retention than did patients with mild skin symptoms (Mann-Whitney U analysis, P = 0.053) or with other background disease (P = 0.0082). Patients with severe skin rash also had longer durations (P = 0.035). In one case, acute urinary retention occurred as late as 19 days after the onset of skin rash. In immune compromised subjects, attention should be paid to patients with herpes zoster in the lumbo-sacral area for late onset of acute urinary retention even after the resolution of skin symptoms.

Ecological transition predictably associated with gene degeneration.

Science.gov (United States)

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil Exantema após vacinação do sarampo: análise laboratorial de casos notificados em São Paulo

Directory of Open Access Journals (Sweden)

Maria I Oliveira

2002-04-01

Full Text Available OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19 using ELISA commercial techniques, and human herpes virus 6 (HHV 6 using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR. RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months, had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17 HPV B19 infection; 76.5% (13 in 17 HHV 6 infection; 5.9% (1 in 17 rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.OBJETIVO: O diagnóstico diferencial de doenças exantemáticas causadas por vírus é geralmente difícil, e equívocos não são raros, especialmente depois da introdução da vacina contra o sarampo e a rubéola. Um estudo laboratorial foi conduzido com o objetivo de estabelecer o diagnóstico etiológico de casos de exantema em crianças que receberam a vacina contra o sarampo. MÉTODOS: Soros de casos de exantema em crianças que

Brain-predicted age in Down syndrome is associated with beta amyloid deposition and cognitive decline.

Science.gov (United States)

Cole, James H; Annus, Tiina; Wilson, Liam R; Remtulla, Ridhaa; Hong, Young T; Fryer, Tim D; Acosta-Cabronero, Julio; Cardenas-Blanco, Arturo; Smith, Robert; Menon, David K; Zaman, Shahid H; Nestor, Peter J; Holland, Anthony J

2017-08-01

Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score. DS participants also underwent [ 11 C]-PiB positron emission tomography (PET) scans to index the levels of cerebral beta amyloid deposition, and cognitive assessment. Mean brain-PAD in DS participants' was +2.49 years, significantly greater than controls (p brain-PAD was associated with the presence and the magnitude of PiB-binding and levels of cognitive performance. Our study indicates that DS is associated with premature structural brain aging, and that age-related alterations in brain structure are associated with individual differences in the rate of beta amyloid deposition and cognitive impairment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Predicting microRNA-disease associations using label propagation based on linear neighborhood similarity.

Science.gov (United States)

Li, Guanghui; Luo, Jiawei; Xiao, Qiu; Liang, Cheng; Ding, Pingjian

2018-05-12

Interactions between microRNAs (miRNAs) and diseases can yield important information for uncovering novel prognostic markers. Since experimental determination of disease-miRNA associations is time-consuming and costly, attention has been given to designing efficient and robust computational techniques for identifying undiscovered interactions. In this study, we present a label propagation model with linear neighborhood similarity, called LPLNS, to predict unobserved miRNA-disease associations. Additionally, a preprocessing step is performed to derive new interaction likelihood profiles that will contribute to the prediction since new miRNAs and diseases lack known associations. Our results demonstrate that the LPLNS model based on the known disease-miRNA associations could achieve impressive performance with an AUC of 0.9034. Furthermore, we observed that the LPLNS model based on new interaction likelihood profiles could improve the performance to an AUC of 0.9127. This was better than other comparable methods. In addition, case studies also demonstrated our method's outstanding performance for inferring undiscovered interactions between miRNAs and diseases, especially for novel diseases. Copyright © 2018. Published by Elsevier Inc.

SNP-associations and phenotype predictions from hundreds of microbial genomes without genome alignments.

Science.gov (United States)

Hall, Barry G

2014-01-01

SNP-association studies are a starting point for identifying genes that may be responsible for specific phenotypes, such as disease traits. The vast bulk of tools for SNP-association studies are directed toward SNPs in the human genome, and I am unaware of any tools designed specifically for such studies in bacterial or viral genomes. The PPFS (Predict Phenotypes From SNPs) package described here is an add-on to kSNP , a program that can identify SNPs in a data set of hundreds of microbial genomes. PPFS identifies those SNPs that are non-randomly associated with a phenotype based on the χ² probability, then uses those diagnostic SNPs for two distinct, but related, purposes: (1) to predict the phenotypes of strains whose phenotypes are unknown, and (2) to identify those diagnostic SNPs that are most likely to be causally related to the phenotype. In the example illustrated here, from a set of 68 E. coli genomes, for 67 of which the pathogenicity phenotype was known, there were 418,500 SNPs. Using the phenotypes of 36 of those strains, PPFS identified 207 diagnostic SNPs. The diagnostic SNPs predicted the phenotypes of all of the genomes with 97% accuracy. It then identified 97 SNPs whose probability of being causally related to the pathogenic phenotype was >0.999. In a second example, from a set of 116 E. coli genome sequences, using the phenotypes of 65 strains PPFS identified 101 SNPs that predicted the source host (human or non-human) with 90% accuracy.

Deep mining heterogeneous networks of biomedical linked data to predict novel drug-target associations.

Science.gov (United States)

Zong, Nansu; Kim, Hyeoneui; Ngo, Victoria; Harismendy, Olivier

2017-08-01

A heterogeneous network topology possessing abundant interactions between biomedical entities has yet to be utilized in similarity-based methods for predicting drug-target associations based on the array of varying features of drugs and their targets. Deep learning reveals features of vertices of a large network that can be adapted in accommodating the similarity-based solutions to provide a flexible method of drug-target prediction. We propose a similarity-based drug-target prediction method that enhances existing association discovery methods by using a topology-based similarity measure. DeepWalk, a deep learning method, is adopted in this study to calculate the similarities within Linked Tripartite Network (LTN), a heterogeneous network generated from biomedical linked datasets. This proposed method shows promising results for drug-target association prediction: 98.96% AUC ROC score with a 10-fold cross-validation and 99.25% AUC ROC score with a Monte Carlo cross-validation with LTN. By utilizing DeepWalk, we demonstrate that: (i) this method outperforms other existing topology-based similarity computation methods, (ii) the performance is better for tripartite than with bipartite networks and (iii) the measure of similarity using network topology outperforms the ones derived from chemical structure (drugs) or genomic sequence (targets). Our proposed methodology proves to be capable of providing a promising solution for drug-target prediction based on topological similarity with a heterogeneous network, and may be readily re-purposed and adapted in the existing of similarity-based methodologies. The proposed method has been developed in JAVA and it is available, along with the data at the following URL: https://github.com/zongnansu1982/drug-target-prediction . nazong@ucsd.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Legionella feeleii: an unusual organism associated with cutaneous infection in an immunocompromised patient.

Science.gov (United States)

Verykiou, S; Goodhead, C; Parry, G; Meggitt, S

2018-04-01

We report a 23-year-old immunocompromised woman who, following cardiac transplantation, presented with an unusual cutaneous eruption. She developed a widespread pustular rash, systemic symptoms and a high temperature with raised inflammatory markers. The diagnosis was reached when a skin biopsy was cultured onto Legionella agar (buffered charcoal yeast extract) and Legionella feeleii was isolated. The patient was treated with 6 weeks of moxifloxacin and her cutaneous lesions gradually resolved. Cutaneous Legionella infections are uncommon and usually affect immunocompromised patients. © 2017 British Association of Dermatologists.

Prediction of medication non-adherence and associated outcomes in pediatric kidney transplant recipients.

Science.gov (United States)

Connelly, James; Pilch, N; Oliver, M; Jordan, C; Fleming, J; Meadows, H; Baliga, P; Nadig, S; Twombley, K; Shatat, I; Taber, D

2015-08-01

Studies have continued to evaluate risk factors associated with post-transplant non-adherence in pediatric patients. However, many of these studies fail to evaluate how risk factors can be utilized to predict MNA. The aims of this study were to (i) determine salient risk factors associated with MNA to develop an adequate predictive risk model and (ii) assess transplant outcomes based on the presence of MNA in a large, diverse cohort of pediatric KTX recipients. One hundred and seventy-five solitary pediatric KTX recipients transplanted from 1999 to 2013 were included. AA, males, older patients, those who lived in urban environments, had legal issues, and lived shorter distances from the transplant center were more likely to have MNA. Using logistic regression, a parsimonious model applying nine risk factors together was developed for predicting MNA, demonstrating a PPV of 69% and a NPV of 81%. Patients with MNA had more than twice the risk of biopsy proven acute rejection, 1.6 times the risk of hospitalization, and 1.8 times the risk of graft loss. Utilization of a predictive model to determine risk of MNA after pediatric KTX may offer clinicians the ability to efficiently and effectively monitor MNA following transplant. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perceived Threat Associated with Police Officers and Black Men Predicts Support for Policing Policy Reform

Directory of Open Access Journals (Sweden)

Allison Louise Skinner

2016-07-01

Full Text Available Racial disparities in policing and recent high-profile incidents resulting in the deaths of Black men have ignited a national debate on policing policies. Given evidence that both police officers and Black men may be associated with threat, we examined the impact of perceived threat on support for reformed policing policies. Across three studies we found correlational evidence that perceiving police officers as threatening predicts increased support for reformed policing practices (e.g., limiting the use of lethal force and matching police force demographics to those of the community. In contrast, perceiving Black men as threatening predicted reduced support for policing policy reform. Perceived threat also predicted willingness to sign a petition calling for police reform. Experimental evidence indicated that priming participants to associate Black men with threat could also reduce support for policing policy reform, and this effect was moderated by internal motivation to respond without prejudice. Priming participants to associate police officers with threat did not increase support for policing policy reform. Results indicate that resistance to policing policy reform is associated with perceiving Black men as threatening. Moreover, findings suggest that publicizing racially charged police encounters, which may conjure associations between Black men and threat, could reduce support for policing policy reform.

Acute encephalitis associated with measles: MRI features

Energy Technology Data Exchange (ETDEWEB)

Lee, K.Y.; Cho, W.H.; Kim, S.H. [Department of Radiology, Sanggye Paik Hospital, Inje University, 760-1 Sanggye-7 dong, Nowon-gu, Seoul 139707 (Korea); Kim, H.D. [Department of Paediatrics, Sanggye Paik Hospital, Inje University, 760-1 Sanggye-7 dong, Nowon-gu, Seoul 139707 (Korea); Kim, I.O. [Department of Radiology, Seoul National University Hospital, 28, Yongon-dong, Chongno-gu, Seoul 110744 (Korea)

2003-02-01

We document the MRI features in six patients aged 5-14 years with acute encephalitis following measles. The diagnosis was made on a characteristic morbiliform rash and detection of specific IgM and IgG antibodies. The symptoms of encephalitis occurred 1-11 days after the appearance of the rash. All patients underwent MRI within 1-4 days of the onset of neurological symptoms. Diffusion weighted images (DWI) were obtained in three patients. In all patients, T2-weighted images showed widely distributed, multifocal high signal in both cerebral hemispheres with swelling of the cortex, with bilateral, symmetrical involvement of the putamen and caudate nucleus. The lesions had showed low apparent diffusion coefficients. Three patients showed subacute gyriform haemorrhage, and asymmetrical gyriform contrast enhancement on follow-up MRI. (orig.)

Child allergic symptoms and mental well-being: the role of maternal anxiety and depression.

Science.gov (United States)

Teyhan, Alison; Galobardes, Bruna; Henderson, John

2014-09-01

To determine whether maternal mental health mediates the relationship between eczema or asthma symptoms and mental well-being in children. Analysis of 7250 children from the Avon Longitudinal Study of Parents and Children. Child mental well-being at 8 years was measured by the Strengths and Difficulties Questionnaire. Binary outcomes were high 'internalizing' (anxious/depressive) and 'externalizing' (oppositional/hyperactive) problems (high was >90th percentile). Child rash and wheeze categories were 'none'; 'early onset transient' (infancy/preschool only); 'persistent' (infancy/preschool and at school age); and 'late onset' (school age only). Maternal anxiety and depression were reported during pregnancy and when child was 8 years old. Persistent wheezing symptoms were associated with high externalizing (OR 1.74, 95% CI, 1.41-2.15) and internalizing (1.67, 1.35-2.06) problems compared with never wheeze. Maternal anxiety and depression, and disrupted child sleep, attenuated these associations. Persistent rash (externalizing: 1.74, 1.40-2.15; internalizing: 1.42, 1.16-1.74) and late onset rash (externalizing: 1.62, 1.17-2.25; internalizing: 1.46, 1.07-1.99) symptoms were associated with poorer mental well-being compared with no rash at any age. Maternal anxiety and depression, particularly when child was aged 8 years rather than during pregnancy, accounted for the association with internalizing symptoms and partly for externalizing symptoms. Sleep disruption did not mediate the association. Maternal anxiety and depression may mediate the association between child rash and wheeze and child mental well-being. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

Science.gov (United States)

Hales, J. B.

2011-01-01

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study

OpenAIRE

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

Background No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Methods Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; th...

Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

Science.gov (United States)

Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

2011-01-01

Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa.

Science.gov (United States)

DeGuzman, Marisa; Shott, Megan E; Yang, Tony T; Riederer, Justin; Frank, Guido K W

2017-06-01

Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration. Female adolescents with anorexia nervosa (N=21; mean age, 16.4 years [SD=1.9]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 15.2 years [SD=2.4]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness. Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response. Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs.

Toxic epidermal necrolysis due to concomitant use of lamotrigine and valproic acid

Directory of Open Access Journals (Sweden)

Sukhjot Kaur

2013-01-01

Full Text Available Anti-epileptic drugs can be associated with a wide spectrum of cutaneous adverse reactions ranging from simple maculopapular rashes to more severe and life threatening reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis. These rashes are well documented with older antiepileptic drugs like phenytoin, phenobarbitone and carbamazapine. Lamotrigine is a newer, unrelated antiepileptic drug that causes skin rashes in 3-10% of new users. Higher starting dose or rapid escalation, concurrent treatment with valproic acid, and a previous history of a rash with other antiepileptic drugs are well recognized risk factors for lamotrigine related serious rashes. We report two patients with toxic epidermal necrolysis, resulting from concomitant use of lamotrigine and valproic acid. It is emphasized that clinicians adhere to the recommended dosage guidelines and adopt a slow dose titration when initiating treatment with lamotrigine.

Prediction of the association state of insulin using spectral parameters.

Science.gov (United States)

Uversky, Vladimir N; Garriques, Liza Nielsen; Millett, Ian S; Frokjaer, Sven; Brange, Jens; Doniach, Sebastian; Fink, Anthony L

2003-04-01

Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The mutants showed different degrees of association (monomer, dimers, tetramers, and hexamers) at neutral pH. A correlation was shown between the accessibility of tyrosines to acrylamide quenching and the degree of association of the insulin mutants. The near-UV CD spectra of the insulins were affected by protein association and by mutation-induced structural perturbations. However, the shape and intensity of difference CD spectra, obtained by subtraction of the spectra measured in 20% acetic acid (where all insulin species were monomeric) from the corresponding spectra measured at neutral pH, correlate well with the degree of insulin association. In fact, the near-UV CD difference spectra for monomeric, dimeric, tetrameric, and hexameric insulin are very distinctive, both in terms of intensity and shape. The results show that the spectral properties of the insulins reflect their state of association, and can be used to predict their oligomeric state. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:847-858, 2003

Prediction of microbe-disease association from the integration of neighbor and graph with collaborative recommendation model.

Science.gov (United States)

Huang, Yu-An; You, Zhu-Hong; Chen, Xing; Huang, Zhi-An; Zhang, Shanwen; Yan, Gui-Ying

2017-10-16

Accumulating clinical researches have shown that specific microbes with abnormal levels are closely associated with the development of various human diseases. Knowledge of microbe-disease associations can provide valuable insights for complex disease mechanism understanding as well as the prevention, diagnosis and treatment of various diseases. However, little effort has been made to predict microbial candidates for human complex diseases on a large scale. In this work, we developed a new computational model for predicting microbe-disease associations by combining two single recommendation methods. Based on the assumption that functionally similar microbes tend to get involved in the mechanism of similar disease, we adopted neighbor-based collaborative filtering and a graph-based scoring method to compute association possibility of microbe-disease pairs. The promising prediction performance could be attributed to the use of hybrid approach based on two single recommendation methods as well as the introduction of Gaussian kernel-based similarity and symptom-based disease similarity. To evaluate the performance of the proposed model, we implemented leave-one-out and fivefold cross validations on the HMDAD database, which is recently built as the first database collecting experimentally-confirmed microbe-disease associations. As a result, NGRHMDA achieved reliable results with AUCs of 0.9023 ± 0.0031 and 0.9111 in the validation frameworks of fivefold CV and LOOCV. In addition, 78.2% microbe samples and 66.7% disease samples are found to be consistent with the basic assumption of our work that microbes tend to get involved in the similar disease clusters, and vice versa. Compared with other methods, the prediction results yielded by NGRHMDA demonstrate its effective prediction performance for microbe-disease associations. It is anticipated that NGRHMDA can be used as a useful tool to search the most potential microbial candidates for various diseases, and therefore

DR2DI: a powerful computational tool for predicting novel drug-disease associations

Science.gov (United States)

Lu, Lu; Yu, Hua

2018-05-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

DR2DI: a powerful computational tool for predicting novel drug-disease associations

Science.gov (United States)

Lu, Lu; Yu, Hua

2018-04-01

Finding the new related candidate diseases for known drugs provides an effective method for fast-speed and low-risk drug development. However, experimental identification of drug-disease associations is expensive and time-consuming. This motivates the need for developing in silico computational methods that can infer true drug-disease pairs with high confidence. In this study, we presented a novel and powerful computational tool, DR2DI, for accurately uncovering the potential associations between drugs and diseases using high-dimensional and heterogeneous omics data as information sources. Based on a unified and extended similarity kernel framework, DR2DI inferred the unknown relationships between drugs and diseases using Regularized Kernel Classifier. Importantly, DR2DI employed a semi-supervised and global learning algorithm which can be applied to uncover the diseases (drugs) associated with known and novel drugs (diseases). In silico global validation experiments showed that DR2DI significantly outperforms recent two approaches for predicting drug-disease associations. Detailed case studies further demonstrated that the therapeutic indications and side effects of drugs predicted by DR2DI could be validated by existing database records and literature, suggesting that DR2DI can be served as a useful bioinformatic tool for identifying the potential drug-disease associations and guiding drug repositioning. Our software and comparison codes are freely available at https://github.com/huayu1111/DR2DI.

Graph-theoretic measures of multivariate association and prediction

International Nuclear Information System (INIS)

Friedman, J.H.; Rafsky, L.C.

1983-01-01

Interpoint-distance-based graphs can be used to define measures of association that extend Kendall's notion of a generalized correlation coefficient. The authors present particular statistics that provide distribution-free tests of independence sensitive to alternatives involving non-monotonic relationships. Moreover, since ordering plays no essential role, the ideas that fully applicable in a multivariate setting. The authors also define an asymmetric coefficient measuring the extent to which (a vector) X can be used to make single-valued predictions of (a vector) Y. The authors discuss various techniques for proving that such statistics are asymptotically normal. As an example of the effectiveness of their approach, the authors present an application to the examination of residuals from multiple regression. 18 references, 2 figures, 1 table

Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1.

Directory of Open Access Journals (Sweden)

Frank van Leth

2004-10-01

Full Text Available BACKGROUND: Patients infected with HIV-1 initiating antiretroviral therapy (ART containing a non-nucleoside reverse transcriptase inhibitor (NNRTI show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP and efavirenz (EFV. METHODS AND FINDINGS: Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417, or EFV (n = 289 in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c, total cholesterol (TC, TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5% than for patients receiving EFV (33.7%; p = 0.036, while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073, resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (-4.1% and an increase for patients receiving EFV (+5.9%; p < 0.001. The increase of non-HDL-c was smaller for patients receiving NVP (24.7% than for patients receiving EFV (33.6%; p = 0.007, as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001 and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378. These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. CONCLUSION: NVP-containing ART shows larger increases in HDL

Child Allergic Symptoms and Mental Well-Being: The Role of Maternal Anxiety and Depression☆

Science.gov (United States)

Teyhan, Alison; Galobardes, Bruna; Henderson, John

2014-01-01

Objective To determine whether maternal mental health mediates the relationship between eczema or asthma symptoms and mental well-being in children. Study design Analysis of 7250 children from the Avon Longitudinal Study of Parents and Children. Child mental well-being at 8 years was measured by the Strengths and Difficulties Questionnaire. Binary outcomes were high ‘internalizing’ (anxious/depressive) and ‘externalizing’ (oppositional/hyperactive) problems (high was >90th percentile). Child rash and wheeze categories were ‘none’; ‘early onset transient’ (infancy/preschool only); ‘persistent’ (infancy/preschool and at school age); and ‘late onset’ (school age only). Maternal anxiety and depression were reported during pregnancy and when child was 8 years old. Results Persistent wheezing symptoms were associated with high externalizing (OR 1.74, 95% CI, 1.41-2.15) and internalizing (1.67, 1.35-2.06) problems compared with never wheeze. Maternal anxiety and depression, and disrupted child sleep, attenuated these associations. Persistent rash (externalizing: 1.74, 1.40-2.15; internalizing: 1.42, 1.16-1.74) and late onset rash (externalizing: 1.62, 1.17-2.25; internalizing: 1.46, 1.07-1.99) symptoms were associated with poorer mental well-being compared with no rash at any age. Maternal anxiety and depression, particularly when child was aged 8 years rather than during pregnancy, accounted for the association with internalizing symptoms and partly for externalizing symptoms. Sleep disruption did not mediate the association. Conclusions Maternal anxiety and depression may mediate the association between child rash and wheeze and child mental well-being. PMID:24952709

Composition and predicted functional ecology of mussel - associated bacteria in Indonesian marine lakes

NARCIS (Netherlands)

Cleary, D.F.R.; Becking, L.E.; Polonia, A.; Freitas, R.M.; Gomes, N.

2015-01-01

In the present study, we sampled bacterial communities associated with mussels inhabiting two distinct coastal marine ecosystems in Kalimantan, Indonesia, namely, marine lakes and coastal mangroves. We used 16S rRNA gene pyrosequencing and predicted metagenomic analysis to compare microbial

Ink and Holes: Correlates and Predictive Associations of Body Modification among Adolescents

Science.gov (United States)

Dukes, Richard L.; Stein, Judith A.

2011-01-01

We examined correlates and predictive associations of tattoos and body piercings among 1,462 Colorado students in grades 9 to 12. More boys (19%) than girls (17%) reported tattoos, but more girls (42%) than boys (16%) reported piercings (earlobes not included). Older students reported more body modification. Structural equation models showed that…

Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.

Directory of Open Access Journals (Sweden)

Marit G A van Vonderen

2009-05-01

Full Text Available Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir. Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684+/-293 grams (estimated mean+/-standard error of the mean(p = 0.02 up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9+/-8.1 cm(2, p = 0.008. In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1+/-0.2 versus 5.3+/-0.2 and 3.6+/-0.1 versus 2.8+/-0.1 mmol/l respectively, p<0.05. Virologic response and safety were comparable in both groups.Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal

Annotating Diseases Using Human Phenotype Ontology Improves Prediction of Disease-Associated Long Non-coding RNAs.

Science.gov (United States)

Le, Duc-Hau; Dao, Lan T M

2018-05-23

Recently, many long non-coding RNAs (lncRNAs) have been identified and their biological function has been characterized; however, our understanding of their underlying molecular mechanisms related to disease is still limited. To overcome the limitation in experimentally identifying disease-lncRNA associations, computational methods have been proposed as a powerful tool to predict such associations. These methods are usually based on the similarities between diseases or lncRNAs since it was reported that similar diseases are associated with functionally similar lncRNAs. Therefore, prediction performance is highly dependent on how well the similarities can be captured. Previous studies have calculated the similarity between two diseases by mapping exactly each disease to a single Disease Ontology (DO) term, and then use a semantic similarity measure to calculate the similarity between them. However, the problem of this approach is that a disease can be described by more than one DO terms. Until now, there is no annotation database of DO terms for diseases except for genes. In contrast, Human Phenotype Ontology (HPO) is designed to fully annotate human disease phenotypes. Therefore, in this study, we constructed disease similarity networks/matrices using HPO instead of DO. Then, we used these networks/matrices as inputs of two representative machine learning-based and network-based ranking algorithms, that is, regularized least square and heterogeneous graph-based inference, respectively. The results showed that the prediction performance of the two algorithms on HPO-based is better than that on DO-based networks/matrices. In addition, our method can predict 11 novel cancer-associated lncRNAs, which are supported by literature evidence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing the simulation and prediction of rainfall associated with the MJO in the POAMA seasonal forecast system

Energy Technology Data Exchange (ETDEWEB)

Marshall, Andrew G. [Centre for Australian Weather and Climate Research, CSIRO Marine and Atmospheric Research, Hobart, (Australia); Hudson, Debra; Wheeler, Matthew C.; Hendon, Harry H.; Alves, Oscar [Centre for Australian Weather and Climate Research, Bureau of Meteorology, Melbourne (Australia)

2011-12-15

We assess the ability of the Predictive Ocean Atmosphere Model for Australia (POAMA) to simulate and predict weekly rainfall associated with the MJO using a 27-year hindcast dataset. After an initial 2-week atmospheric adjustment, the POAMA model is shown to simulate well, both in pattern and in intensity, the weekly-mean rainfall variation associated with the evolution of the MJO over the tropical Indo-Pacific. The simulation is most realistic in December-February (austral summer) and least realistic in March-May (austral autumn). Regionally, the most problematic area is the Maritime Continent, which is a common problem area in other models. Coupled with our previous demonstration of the ability of POAMA to predict the evolution of the large-scale structure of the MJO for up to about 3 weeks, this ability to simulate the regional rainfall evolution associated with the MJO translates to enhanced predictability of rainfall regionally throughout much of the tropical Indo-Pacific when the MJO is present in the initial conditions during October-March. We also demonstrate enhanced prediction skill of rainfall at up to 3 weeks lead time over the north-east Pacific and north Atlantic, which are areas of pronounced teleconnections excited by the MJO-modulation of tropical Indo-Pacific rainfall. Failure to simulate and predict the modulation of rainfall in such places as the Maritime Continent and tropical Australia by the MJO indicates, however, there is still much room for improvement of the prediction of the MJO and its teleconnections. (orig.)

Differential RISC association of endogenous human microRNAs predicts their inhibitory potential.

Science.gov (United States)

Flores, Omar; Kennedy, Edward M; Skalsky, Rebecca L; Cullen, Bryan R

2014-04-01

It has previously been assumed that the generally high stability of microRNAs (miRNAs) reflects their tight association with Argonaute (Ago) proteins, essential components of the RNA-induced silencing complex (RISC). However, recent data have suggested that the majority of mature miRNAs are not, in fact, Ago associated. Here, we demonstrate that endogenous human miRNAs vary widely, by >100-fold, in their level of RISC association and show that the level of Ago binding is a better indicator of inhibitory potential than is the total level of miRNA expression. While miRNAs of closely similar sequence showed comparable levels of RISC association in the same cell line, these varied between different cell types. Moreover, the level of RISC association could be modulated by overexpression of complementary target mRNAs. Together, these data indicate that the level of RISC association of a given endogenous miRNA is regulated by the available RNA targetome and predicts miRNA function.

Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer

Directory of Open Access Journals (Sweden)

Jitka eFucikova

2015-08-01

Full Text Available It is now clear that human neoplasms form, progress and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (reactivation of tumor-targeting immune response. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as „immunogenic cell death (ICD. Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as „damage-associated molecular patterns (DAMPs, may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.

The sweet Christmas rash (case series)

DEFF Research Database (Denmark)

Gyldenløve, Mette; Nepper-Christensen, Steen; Thyssen, Jacob P

2013-01-01

Christmas tree hypersensitivity is a rare condition, which has so far obtained scarce attention in the medical literature. We present two clinical cases of hypersensitivity associated with Christmas tree exposure, a 51-year-old woman with allergic contact dermatitis and a 41-year-old man...... with allergic rhinitis. The female patient had a positive patch test reaction to colophony, and the male patient had a positive skin prick test reaction to alternaria mould. Both were successfully advised to avoid prolonged exposure to Christmas trees and buy artificial trees for Christmas....

The Spike-and-Slab Lasso Generalized Linear Models for Prediction and Associated Genes Detection.

Science.gov (United States)

Tang, Zaixiang; Shen, Yueping; Zhang, Xinyan; Yi, Nengjun

2017-01-01

Large-scale "omics" data have been increasingly used as an important resource for prognostic prediction of diseases and detection of associated genes. However, there are considerable challenges in analyzing high-dimensional molecular data, including the large number of potential molecular predictors, limited number of samples, and small effect of each predictor. We propose new Bayesian hierarchical generalized linear models, called spike-and-slab lasso GLMs, for prognostic prediction and detection of associated genes using large-scale molecular data. The proposed model employs a spike-and-slab mixture double-exponential prior for coefficients that can induce weak shrinkage on large coefficients, and strong shrinkage on irrelevant coefficients. We have developed a fast and stable algorithm to fit large-scale hierarchal GLMs by incorporating expectation-maximization (EM) steps into the fast cyclic coordinate descent algorithm. The proposed approach integrates nice features of two popular methods, i.e., penalized lasso and Bayesian spike-and-slab variable selection. The performance of the proposed method is assessed via extensive simulation studies. The results show that the proposed approach can provide not only more accurate estimates of the parameters, but also better prediction. We demonstrate the proposed procedure on two cancer data sets: a well-known breast cancer data set consisting of 295 tumors, and expression data of 4919 genes; and the ovarian cancer data set from TCGA with 362 tumors, and expression data of 5336 genes. Our analyses show that the proposed procedure can generate powerful models for predicting outcomes and detecting associated genes. The methods have been implemented in a freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). Copyright © 2017 by the Genetics Society of America.

Predictive factors associated with death of elderly in nursing homes.

Science.gov (United States)

Sung, Kiwol

2014-06-01

An increasing elderly population reflects a great need for readily accessible, clinically useful methods to identify mortality-related factors in nursing home residents. The purpose of this study was to identify factors associated with the deaths of nursing home residents. Data was collected from a Minimal Data Set of 195 elderly nursing home residents, followed by analysis of demographic factors, disease and nursing condition factors, Activities of Daily Living (ADL), cognitive function, behavioral patterns, and dysfunctional status. Major factors associated with death among nursing home residents were identified as dyspnea (odds ratio [OR] = 4.88), problematic behaviors (OR = 3.95), and ADL (OR = 3.61). These variables accounted for 31.1% of the variance in death. Dyspnea, problematic behaviors, and ADL data were identified as the key factors associated with death among nursing home residents. Future plans for the prediction of death among nursing home residents can be made by nursing staff, factoring in these identified variables, to ensure more comfortable conditions and more responsive care. Copyright © 2014. Published by Elsevier B.V.

Rubella associated with hemophagocytic syndrome. First report in a male and review of the literature

Directory of Open Access Journals (Sweden)

Makram Koubaa

2012-08-01

Full Text Available A 22-year-old man was admitted to our hospital because of fever, skin rash and epistaxis. Physical examination revealed fever (39.5°C, generalized purpura, lymphadenopathy and splenomegaly. Blood tests showed pancytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis with no evidence of malignant cells. Anti rubella IgM antibody were positif and the IgG titers increased from 16 to 50 UI/mL in 3 days. Therefore, he was diagnosed to have rubella-associated hemophagocytic syndrome. We report herein the first case in a man and the sixth case of rubella-associated hemophagocytic syndrome in the literature by search in Pub Med till March 2012.

Predictive modelling of Ross River virus notifications in southeastern Australia.

Science.gov (United States)

Cutcher, Z; Williamson, E; Lynch, S E; Rowe, S; Clothier, H J; Firestone, S M

2017-02-01

Ross River virus (RRV) is a mosquito-borne virus endemic to Australia. The disease, marked by arthritis, myalgia and rash, has a complex epidemiology involving several mosquito species and wildlife reservoirs. Outbreak years coincide with climatic conditions conducive to mosquito population growth. We developed regression models for human RRV notifications in the Mildura Local Government Area, Victoria, Australia with the objective of increasing understanding of the relationships in this complex system, providing trigger points for intervention and developing a forecast model. Surveillance, climatic, environmental and entomological data for the period July 2000-June 2011 were used for model training then forecasts were validated for July 2011-June 2015. Rainfall and vapour pressure were the key factors for forecasting RRV notifications. Validation of models showed they predicted RRV counts with an accuracy of 81%. Two major RRV mosquito vectors (Culex annulirostris and Aedes camptorhynchus) were important in the final estimation model at proximal lags. The findings of this analysis advance understanding of the drivers of RRV in temperate climatic zones and the models will inform public health agencies of periods of increased risk.

Network-based ranking methods for prediction of novel disease associated microRNAs.

Science.gov (United States)

Le, Duc-Hau

2015-10-01

Many studies have shown roles of microRNAs on human disease and a number of computational methods have been proposed to predict such associations by ranking candidate microRNAs according to their relevance to a disease. Among them, machine learning-based methods usually have a limitation in specifying non-disease microRNAs as negative training samples. Meanwhile, network-based methods are becoming dominant since they well exploit a "disease module" principle in microRNA functional similarity networks. Of which, random walk with restart (RWR) algorithm-based method is currently state-of-the-art. The use of this algorithm was inspired from its success in predicting disease gene because the "disease module" principle also exists in protein interaction networks. Besides, many algorithms designed for webpage ranking have been successfully applied in ranking disease candidate genes because web networks share topological properties with protein interaction networks. However, these algorithms have not yet been utilized for disease microRNA prediction. We constructed microRNA functional similarity networks based on shared targets of microRNAs, and then we integrated them with a microRNA functional synergistic network, which was recently identified. After analyzing topological properties of these networks, in addition to RWR, we assessed the performance of (i) PRINCE (PRIoritizatioN and Complex Elucidation), which was proposed for disease gene prediction; (ii) PageRank with Priors (PRP) and K-Step Markov (KSM), which were used for studying web networks; and (iii) a neighborhood-based algorithm. Analyses on topological properties showed that all microRNA functional similarity networks are small-worldness and scale-free. The performance of each algorithm was assessed based on average AUC values on 35 disease phenotypes and average rankings of newly discovered disease microRNAs. As a result, the performance on the integrated network was better than that on individual ones. In

Probabilistic Category Learning in Developmental Dyslexia: Evidence from Feedback and Paired-Associate Weather Prediction Tasks

Science.gov (United States)

Gabay, Yafit; Vakil, Eli; Schiff, Rachel; Holt, Lori L.

2015-01-01

Objective Developmental dyslexia is presumed to arise from specific phonological impairments. However, an emerging theoretical framework suggests that phonological impairments may be symptoms stemming from an underlying dysfunction of procedural learning. Method We tested procedural learning in adults with dyslexia (n=15) and matched-controls (n=15) using two versions of the Weather Prediction Task: Feedback (FB) and Paired-associate (PA). In the FB-based task, participants learned associations between cues and outcomes initially by guessing and subsequently through feedback indicating the correctness of response. In the PA-based learning task, participants viewed the cue and its associated outcome simultaneously without overt response or feedback. In both versions, participants trained across 150 trials. Learning was assessed in a subsequent test without presentation of the outcome, or corrective feedback. Results The Dyslexia group exhibited impaired learning compared with the Control group on both the FB and PA versions of the weather prediction task. Conclusions The results indicate that the ability to learn by feedback is not selectively impaired in dyslexia. Rather it seems that the probabilistic nature of the task, shared by the FB and PA versions of the weather prediction task, hampers learning in those with dyslexia. Results are discussed in light of procedural learning impairments among participants with dyslexia. PMID:25730732

Esophageal Stenosis Associated With Tumor Regression in Radiotherapy for Esophageal Cancer: Frequency and Prediction

Energy Technology Data Exchange (ETDEWEB)

Atsumi, Kazushige [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Arimura, Hidetaka [Department of Health Sciences, Kyushu University, Fukuoka (Japan); Terashima, Kotaro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Matsuki, Takaomi [Department of Health Sciences, Kyushu University, Fukuoka (Japan); Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Nakamura, Katsumasa [Department of Radiology, Kyushu University Hospital at Beppu, Oita (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

2012-04-01

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

Science.gov (United States)

Shlay, Judith C; Sharma, Shweta; Peng, Grace; Gibert, Cynthia L; Grunfeld, Carl

2009-07-01

To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

DRESS syndrome associated with type 2 diabetes in a child

Science.gov (United States)

Erdem, Semiha Bahceci; Bag, Ozlem; Karkiner, Canan Sule Unsal; Korkmaz, Huseyin Anil; Can, Demet

2016-01-01

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to “drug rash with eosinophilia and systemic symptoms syndrome” such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID:26862317

Prediction-based association control scheme in dense femtocell networks

Science.gov (United States)

Pham, Ngoc-Thai; Huynh, Thong; Hwang, Won-Joo; You, Ilsun; Choo, Kim-Kwang Raymond

2017-01-01

The deployment of large number of femtocell base stations allows us to extend the coverage and efficiently utilize resources in a low cost manner. However, the small cell size of femtocell networks can result in frequent handovers to the mobile user, and consequently throughput degradation. Thus, in this paper, we propose predictive association control schemes to improve the system’s effective throughput. Our design focuses on reducing handover frequency without impacting on throughput. The proposed schemes determine handover decisions that contribute most to the network throughput and are proper for distributed implementations. The simulation results show significant gains compared with existing methods in terms of handover frequency and network throughput perspective. PMID:28328992

Interannual Variability, Global Teleconnection, and Potential Predictability Associated with the Asian Summer Monsoon

Science.gov (United States)

Lau, K. M.; Kim, K. M.; Li, J. Y.

2001-01-01

In this Chapter, aspects of global teleconnections associated with the interannual variability of the Asian summer monsoon (ASM) are discussed. The basic differences in the basic dynamics of the South Asian Monsoon and the East Asian monsoon, and their implications on global linkages are discussed. Two teleconnection modes linking ASM variability to summertime precipitation over the continental North America were identified. These modes link regional circulation and precipitation anomalies over East Asia and continental North America, via coupled atmosphere-ocean variations over the North Pacific. The first mode has a large zonally symmetrical component and appears to be associated with subtropical jetstream variability and the second mode with Rossby wave dispersion. Both modes possess strong sea surface temperature (SST) expressions in the North Pacific. Results show that the two teleconnection modes may have its origin in intrinsic modes of sea surface temperature variability in the extratropical oceans, which are forced in part by atmospheric variability and in part by air-sea interaction. The potential predictability of the ASM associated with SST variability in different ocean basins is explored using a new canonical ensemble correlation prediction scheme. It is found that SST anomalies in tropical Pacific, i.e., El Nino, is the most dominant forcing for the ASM, especially over the maritime continent and eastern Australia. SST anomalies in the India Ocean may trump the influence from El Nino in western Australia and western maritime continent. Both El Nino, and North Pacific SSTs contribute to monsoon precipitation anomalies over Japan, southern Korea, northern and central China. By optimizing SST variability signals from the world ocean basins using CEC, the overall predictability of ASM can be substantially improved.

Fatal nevirapine-induced Stevens- Johnson syndrome with HIV ...

African Journals Online (AJOL)

2014-06-01

Jun 1, 2014 ... of Stevens-Johnson syndrome highlights the dilemmas and complications that may arise when prescribing multiple medications in HIV-associated ... HIV enters the central nervous system early in the course of HIV ... Affected individuals with SJS/TEN are genetically predisposed to developing severe ...

Heat Rash

Science.gov (United States)

... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life Issues Insurance & Bills Self Care Working With Your Doctor Drugs, Procedures & Devices Over-the- ...

Association of Sweet's Syndrome and Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

J. L. Barton

2011-01-01

Full Text Available Sweet's syndrome is an acute febrile neutrophilic dermatosis which usually presents as an idiopathic disorder but can also be drug induced, associated with hematopoetic malignancies and myelodysplastic disorders, and more, infrequently, observed in autoimmune disorders. Sweet's syndrome has been reported in three cases of neonatal lupus, three cases of hydralazine-induced lupus in adults, and in nine pediatric and adult systemic lupus erythematosus (SLE patients. We describe three additional adult cases of Sweet's associated with SLE and provide a focused review on nondrug-induced, nonneonatal SLE and Sweet's. In two of three new cases, as in the majority of prior cases, the skin rash of Sweet's paralleled underlying SLE disease activity. The pathogenesis of Sweet's remains elusive, but evidence suggests that cytokine dysregulation may be central to the clinical and pathological changes in this condition, as well as in SLE. Further research is needed to define the exact relationship between the two conditions.

Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

Science.gov (United States)

Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

2003-01-01

HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

Sympatry Predicts Spot Pigmentation Patterns and Female Association Behavior in the Livebearing Fish Poeciliopsis baenschi

Science.gov (United States)

Roth-Monzón, Andrea J.; Scott, Laura E.; Camargo, Ashley A.; Clark, Eliza I.; Schott, Eric E.; Johnson, Jerald B.

2017-01-01

In this study, we explored the possibility that differences in pigmentation patterns among populations of the fish Poeciliopsis baenschi were associated with the presence or absence of the closely related species P. turneri. If reproductive character displacement is responsible, spotting patterns in these two species should diverge in sympatry, but not allopatry. We predicted that female P. baenschi from sympatric sites should show a preference for associating with conspecifics vs. heterospecific males, but females from allopatric sites should show no such preferences. To evaluate these predictions, we compared spotting patterns and female association behaviors in populations of P. baenschi from Central Mexico. We found that both of our predictions were supported. Poeciliopsis baenschi that co-occured with P. turneri had spotting patterns significantly different than their counterparts from allopatric sites. Using a simultaneous choice test of video presentations of males, we also found that female P. baenschi from populations that co-occured with P. turneri spent significantly more time with males of their own species than with P. turneri males. In contrast, females from allopatric populations of P. baenschi showed no differences in the amount of time they spent with either conspecific or heterospecific males. Together, our results are consistent with the hypothesis that reproductive character displacement may be responsible for behavioral and spotting pattern differences in these populations of P. baenschi. PMID:28107407

Association of grey matter changes with stability and flexibility of prediction in akinetic-rigid Parkinson's disease.

Science.gov (United States)

Trempler, Ima; Binder, Ellen; El-Sourani, Nadiya; Schiffler, Patrick; Tenberge, Jan-Gerd; Schiffer, Anne-Marike; Fink, Gereon R; Schubotz, Ricarda I

2018-06-01

Parkinson's disease (PD), which is caused by degeneration of dopaminergic neurons in the midbrain, results in a heterogeneous clinical picture including cognitive decline. Since the phasic signal of dopamine neurons is proposed to guide learning by signifying mismatches between subjects' expectations and external events, we here investigated whether akinetic-rigid PD patients without mild cognitive impairment exhibit difficulties in dealing with either relevant (requiring flexibility) or irrelevant (requiring stability) prediction errors. Following our previous study on flexibility and stability in prediction (Trempler et al. J Cogn Neurosci 29(2):298-309, 2017), we then assessed whether deficits would correspond with specific structural alterations in dopaminergic regions as well as in inferior frontal cortex, medial prefrontal cortex, and the hippocampus. Twenty-one healthy controls and twenty-one akinetic-rigid PD patients on and off medication performed a task which required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press, whereas sequence omissions had to be ignored. Independent of the disease, midbrain volume was related to a general response bias to unexpected events, whereas right putamen volume correlated with the ability to discriminate between relevant and irrelevant prediction errors. However, patients compared with healthy participants showed deficits in stabilisation against irrelevant prediction errors, associated with thickness of right inferior frontal gyrus and left medial prefrontal cortex. Flexible updating due to relevant prediction errors was also affected in patients compared with controls and associated with right hippocampus volume. Dopaminergic medication influenced behavioural performance across, but not within the patients. Our exploratory study warrants further research on deficient prediction error processing and its structural correlates as a core of cognitive symptoms

Application and comparison of scoring indices to predict outcomes in patients with healthcare-associated pneumonia

OpenAIRE

Fang, Wen-Feng; Yang, Kuang-Yao; Wu, Chieh-Liang; Yu, Chong-Jen; Chen, Chang-Wen; Tu, Chih-Yen; Lin, Meng-Chih

2011-01-01

Introduction Healthcare-associated pneumonia (HCAP) is a relatively new category of pneumonia. It refers to infections that occur prior to hospital admission in patients with specific risk factors following contact or exposure to a healthcare environment. There is currently no scoring index to predict the outcomes of HCAP patients. We applied and compared different community acquired pneumonia (CAP) scoring indices to predict 30-day mortality and 3-day and 14-day intensive care unit (ICU) adm...

Hepatit A geçiren hastada akut ürtiker ve Guillain-Barre like sendromun birlikteliği

OpenAIRE

GERENLİ, Nelgin Esenrodoplu; GÜVEN, Feray; UYGUR, Nihan; AKYÜZ, Ümit; SAY, Aysu

2004-01-01

Hepatitis A infection (HAV) may present with extrahepatic manifestations rather than causing typical hepatitis. These are: urticarial rash, vasculitis, arthritis, transient arthralgia, hemolytic anemia, thrombocytopenia, cryoglobulinemia, . Guillain-Barre Syndrome and polymyositis. We report a case of 4.5 years old boy with a rare association of acute HAV infection and urticarial rash accompanied by Guillain-Barre like Syndrome.

Addressing issues associated with evaluating prediction models for survival endpoints based on the concordance statistic.

Science.gov (United States)

Wang, Ming; Long, Qi

2016-09-01

Prediction models for disease risk and prognosis play an important role in biomedical research, and evaluating their predictive accuracy in the presence of censored data is of substantial interest. The standard concordance (c) statistic has been extended to provide a summary measure of predictive accuracy for survival models. Motivated by a prostate cancer study, we address several issues associated with evaluating survival prediction models based on c-statistic with a focus on estimators using the technique of inverse probability of censoring weighting (IPCW). Compared to the existing work, we provide complete results on the asymptotic properties of the IPCW estimators under the assumption of coarsening at random (CAR), and propose a sensitivity analysis under the mechanism of noncoarsening at random (NCAR). In addition, we extend the IPCW approach as well as the sensitivity analysis to high-dimensional settings. The predictive accuracy of prediction models for cancer recurrence after prostatectomy is assessed by applying the proposed approaches. We find that the estimated predictive accuracy for the models in consideration is sensitive to NCAR assumption, and thus identify the best predictive model. Finally, we further evaluate the performance of the proposed methods in both settings of low-dimensional and high-dimensional data under CAR and NCAR through simulations. © 2016, The International Biometric Society.

Specific predictive power of automatic spider-related affective associations for controllable and uncontrollable fear responses toward spiders

NARCIS (Netherlands)

Huijdlng, J; de Jong, PJ; Huijding, J.

This study examined the predictive power of automatically activated spider-related affective associations for automatic and controllable fear responses. The Extrinsic Affective Simon Task (EAST; De Houwer, 2003) was used to indirectly assess automatic spider fear-related associations. The EAST and

Test-retest reliability and predictive validity of the Implicit Association Test in children.

Science.gov (United States)

Rae, James R; Olson, Kristina R

2018-02-01

The Implicit Association Test (IAT) is increasingly used in developmental research despite minimal evidence of whether children's IAT scores are reliable across time or predictive of behavior. When test-retest reliability and predictive validity have been assessed, the results have been mixed, and because these studies have differed on many factors simultaneously (lag-time between testing administrations, domain, etc.), it is difficult to discern what factors may explain variability in existing test-retest reliability and predictive validity estimates. Across five studies (total N = 519; ages 6- to 11-years-old), we manipulated two factors that have varied in previous developmental research-lag-time and domain. An internal meta-analysis of these studies revealed that, across three different methods of analyzing the data, mean test-retest (rs of .48, .38, and .34) and predictive validity (rs of .46, .20, and .10) effect sizes were significantly greater than zero. While lag-time did not moderate the magnitude of test-retest coefficients, whether we observed domain differences in test-retest reliability and predictive validity estimates was contingent on other factors, such as how we scored the IAT or whether we included estimates from a unique sample (i.e., a sample containing gender typical and gender diverse children). Recommendations are made for developmental researchers that utilize the IAT in their research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

Science.gov (United States)

Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

2011-11-01

Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

Evaluation of DNA variants associated with androgenetic alopecia and their potential to predict male pattern baldness.

Science.gov (United States)

Marcińska, Magdalena; Pośpiech, Ewelina; Abidi, Sarah; Andersen, Jeppe Dyrberg; van den Berge, Margreet; Carracedo, Ángel; Eduardoff, Mayra; Marczakiewicz-Lustig, Anna; Morling, Niels; Sijen, Titia; Skowron, Małgorzata; Söchtig, Jens; Syndercombe-Court, Denise; Weiler, Natalie; Schneider, Peter M; Ballard, David; Børsting, Claus; Parson, Walther; Phillips, Chris; Branicki, Wojciech

2015-01-01

Androgenetic alopecia, known in men as male pattern baldness (MPB), is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies have revealed multiple genes and polymorphisms to be associated with susceptibility to MPB. In this study, 50 candidate SNPs for androgenetic alopecia were analyzed in order to verify their potential to predict MPB. Significant associations were confirmed for 29 SNPs from chromosomes X, 1, 5, 7, 18 and 20. A simple 5-SNP prediction model and an extended 20-SNP model were developed based on a discovery panel of 305 males from various European populations fitting one of two distinct phenotype categories. The first category consisted of men below 50 years of age with significant baldness and the second; men aged 50 years or older lacking baldness. The simple model comprised the five best predictors: rs5919324 near AR, rs1998076 in the 20p11 region, rs929626 in EBF1, rs12565727 in TARDBP and rs756853 in HDAC9. The extended prediction model added 15 SNPs from five genomic regions that improved overall prevalence-adjusted predictive accuracy measured by area under the receiver characteristic operating curve (AUC). Both models were evaluated for predictive accuracy using a test set of 300 males reflecting the general European population. Applying a 65% probability threshold, high prediction sensitivity of 87.1% but low specificity of 42.4% was obtained in men aged <50 years. In men aged ≥50, prediction sensitivity was slightly lower at 67.7% while specificity reached 90%. Overall, the AUC=0.761 calculated for men at or above 50 years of age indicates these SNPs offer considerable potential for the application of genetic tests to predict MPB patterns, adding a highly informative predictive system to the emerging field of forensic analysis of externally visible characteristics.

Evaluation of DNA variants associated with androgenetic alopecia and their potential to predict male pattern baldness.

Directory of Open Access Journals (Sweden)

Magdalena Marcińska

Full Text Available Androgenetic alopecia, known in men as male pattern baldness (MPB, is a very conspicuous condition that is particularly frequent among European men and thus contributes markedly to variation in physical appearance traits amongst Europeans. Recent studies have revealed multiple genes and polymorphisms to be associated with susceptibility to MPB. In this study, 50 candidate SNPs for androgenetic alopecia were analyzed in order to verify their potential to predict MPB. Significant associations were confirmed for 29 SNPs from chromosomes X, 1, 5, 7, 18 and 20. A simple 5-SNP prediction model and an extended 20-SNP model were developed based on a discovery panel of 305 males from various European populations fitting one of two distinct phenotype categories. The first category consisted of men below 50 years of age with significant baldness and the second; men aged 50 years or older lacking baldness. The simple model comprised the five best predictors: rs5919324 near AR, rs1998076 in the 20p11 region, rs929626 in EBF1, rs12565727 in TARDBP and rs756853 in HDAC9. The extended prediction model added 15 SNPs from five genomic regions that improved overall prevalence-adjusted predictive accuracy measured by area under the receiver characteristic operating curve (AUC. Both models were evaluated for predictive accuracy using a test set of 300 males reflecting the general European population. Applying a 65% probability threshold, high prediction sensitivity of 87.1% but low specificity of 42.4% was obtained in men aged <50 years. In men aged ≥50, prediction sensitivity was slightly lower at 67.7% while specificity reached 90%. Overall, the AUC=0.761 calculated for men at or above 50 years of age indicates these SNPs offer considerable potential for the application of genetic tests to predict MPB patterns, adding a highly informative predictive system to the emerging field of forensic analysis of externally visible characteristics.

A Semi-Supervised Learning Algorithm for Predicting Four Types MiRNA-Disease Associations by Mutual Information in a Heterogeneous Network.

Science.gov (United States)

Zhang, Xiaotian; Yin, Jian; Zhang, Xu

2018-03-02

Increasing evidence suggests that dysregulation of microRNAs (miRNAs) may lead to a variety of diseases. Therefore, identifying disease-related miRNAs is a crucial problem. Currently, many computational approaches have been proposed to predict binary miRNA-disease associations. In this study, in order to predict underlying miRNA-disease association types, a semi-supervised model called the network-based label propagation algorithm is proposed to infer multiple types of miRNA-disease associations (NLPMMDA) by mutual information derived from the heterogeneous network. The NLPMMDA method integrates disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity information of miRNAs and diseases to construct a heterogeneous network. NLPMMDA is a semi-supervised model which does not require verified negative samples. Leave-one-out cross validation (LOOCV) was implemented for four known types of miRNA-disease associations and demonstrated the reliable performance of our method. Moreover, case studies of lung cancer and breast cancer confirmed effective performance of NLPMMDA to predict novel miRNA-disease associations and their association types.

Evaluation of the predictive capacity of DNA variants associated with straight hair in Europeans

DEFF Research Database (Denmark)

Pośpiech, Ewelina; Karłowska-Pik, Joanna; Marcińska, Magdalena

2015-01-01

pattern baldness revealed a suggestive association with hair morphology for rs4679955 on 3q25.1. The study results reported provide the starting point for the development of a predictive test for hair morphology in Europeans. More studies are now needed to discover additional determinants of hair...

Development of associations and kinetic models for microbiological data to be used in comprehensive food safety prediction software.

Science.gov (United States)

Halder, Amit; Black, D Glenn; Davidson, P Michael; Datta, Ashim

2010-08-01

The objective of this study was to use an existing database of food products and their associated processes, link it with a list of the foodborne pathogenic microorganisms associated with those products and finally identify growth and inactivation kinetic parameters associated with those pathogens. The database was to be used as a part of the development of comprehensive software which could predict food safety and quality for any food product. The main issues in building such a predictive system included selection of predictive models, associations of different food types with pathogens (as determined from outbreak histories), and variability in data from different experiments. More than 1000 data sets from published literature were analyzed and grouped according to microorganisms and food types. Final grouping of data consisted of the 8 most prevalent pathogens for 14 different food groups, covering all of the foods (>7000) listed in the USDA Natl. Nutrient Database. Data for each group were analyzed in terms of 1st-order inactivation, 1st-order growth, and sigmoidal growth models, and their kinetic response for growth and inactivation as a function of temperature were reported. Means and 95% confidence intervals were calculated for prediction equations. The primary advantage in obtaining group-specific kinetic data is the ability to extend microbiological growth and death simulation to a large array of product and process possibilities, while still being reasonably accurate. Such simulation capability could provide vital ''what if'' scenarios for industry, Extension, and academia in food safety.

STOPGAP: a database for systematic target opportunity assessment by genetic association predictions.

Science.gov (United States)

Shen, Judong; Song, Kijoung; Slater, Andrew J; Ferrero, Enrico; Nelson, Matthew R

2017-09-01

We developed the STOPGAP (Systematic Target OPportunity assessment by Genetic Association Predictions) database, an extensive catalog of human genetic associations mapped to effector gene candidates. STOPGAP draws on a variety of publicly available GWAS associations, linkage disequilibrium (LD) measures, functional genomic and variant annotation sources. Algorithms were developed to merge the association data, partition associations into non-overlapping LD clusters, map variants to genes and produce a variant-to-gene score used to rank the relative confidence among potential effector genes. This database can be used for a multitude of investigations into the genes and genetic mechanisms underlying inter-individual variation in human traits, as well as supporting drug discovery applications. Shell, R, Perl and Python scripts and STOPGAP R data files (version 2.5.1 at publication) are available at https://github.com/StatGenPRD/STOPGAP . Some of the most useful STOPGAP fields can be queried through an R Shiny web application at http://stopgapwebapp.com . matthew.r.nelson@gsk.com. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Prognosis of patients with whiplash-associated disorders consulting physiotherapy: development of a predictive model for recovery

OpenAIRE

Bohman, Tony; C?t?, Pierre; Boyle, Eleanor; Cassidy, J David; Carroll, Linda J; Skillgate, Eva

2012-01-01

Abstract Background Patients with whiplash-associated disorders (WAD) have a generally favourable prognosis, yet some develop longstanding pain and disability. Predicting who will recover from WAD shortly after a traffic collision is very challenging for health care providers such as physical therapists. Therefore, we aimed to develop a prediction model for the recovery of WAD in a cohort of patients who consulted physical therapists within six weeks after the injury. Methods Our cohort inclu...

Abacavir-induced liver toxicity

Directory of Open Access Journals (Sweden)

Maria Diletta Pezzani

2016-09-01

Full Text Available Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Science.gov (United States)

Hofheinz, R-D; Lorenzen, S; Trojan, J; Ocvirk, J; Ettrich, T J; Al-Batran, S-E; Schulz, H; Homann, N; Feustel, H-P; Schatz, M; Kripp, M; Schulte, N; Tetyusheva, M; Heeger, S; Vlassak, S; Merx, K

2018-04-01

Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

An increase in rates of obstetric haemorrhage in a setting of high HIV seroprevalence

Directory of Open Access Journals (Sweden)

E Shabalala

2017-07-01

Full Text Available Background. Obstetric haemorrhage (OH is the leading cause of maternal mortality worldwide, although, indirectly, HIV is also a leading cause of maternal mortality in some settings with a high HIV seroprevalence. Objective. To determine the possible association between increasing rates of OH and HIV or its treatment. Methods. We conducted a retrospective chart review of women with OH at King Edward VIII Hospital, Durban, South Africa, over a 3-year period (2009 - 2011, during which the drug regimen for the prevention of mother-to-child transmission was evolving from single-dose nevirapine to antenatal zidovudine combined with intrapartum nevirapine (also referred to as dual therapy, and finally to a combination or highly active antiretroviral therapy (cART or HAART. Cases of OH (including abruptio placentae, placenta praevia, unspecified antepartum haemorrhage (APH, and postpartum haemorrhage (PPH were identified from maternity delivery records, and the relevant data extracted. Results. We analysed the records of 448 women diagnosed with OH. Even though the incidence of OH was low, the study found an increasing number of cases during the 3-year period. PPH – not APH – was associated with HIV seropositivity (odds ratio 1.84, 95% confi­dence interval 1.14 - 2.95. cART was not associated with an increased risk of haemorrhage. Conclusion. HIV was associated with a high risk of PPH, and its possible association with HIV treatment needs further research.

Lack of Association between an Interleukin-I Receptor Antagonist Gene Polymorphism and Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Victor A. Danis

1994-01-01

Full Text Available Non-MHC linked genes may contribute to genetic predisposition to the development of systemic lupus erythematosus. The possibility that cytokine genes may be involved was raised by the observation of increased frequency in expression of an uncommon allele of an interleukin-I receptor antagonist gene polymorphism and SLE in a recent U.K. study. We have not been able to show any significant differences in expression of this allele in SLE patients as a whole or in any patient subgroups. Our results actually show a slight decrease in the expression of this allele in SLE patients compared with healthy controls and in SLE patients with malar rash compared with SLE patients without malar rash.

Autoimmune Neurological Conditions Associated With Zika Virus Infection

Directory of Open Access Journals (Sweden)

Yeny Acosta-Ampudia

2018-04-01

Full Text Available Zika virus (ZIKV is an emerging flavivirus rapidly spreading throughout the tropical Americas. Aedes mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids. ZIKV infection is often asymptomatic and those with symptoms present minor illness after 3 to 12 days of incubation, characterized by a mild and self-limiting disease with low-grade fever, conjunctivitis, widespread pruritic maculopapular rash, arthralgia and myalgia. ZIKV has been linked to a number of central and peripheral nervous system injuries such as Guillain-Barré syndrome (GBS, transverse myelitis (TM, meningoencephalitis, ophthalmological manifestations, and other neurological complications. Nevertheless, mechanisms of host-pathogen neuro-immune interactions remain incompletely elucidated. This review provides a critical discussion about the possible mechanisms underlying the development of autoimmune neurological conditions associated with Zika virus infection.

Association between sepsis and Rocky Mountain spotted fever.

Science.gov (United States)

Bacci, Marcelo Rodrigues; Namura, José Jorge

2012-12-06

Rocky Mountain spotted fever (RMSF) is a disease caused by the Gram-negative coccobacillus Rickettsia ricketsii which has been on the rise since the last decade in the USA. The symptoms are common to the many viral diseases, and the classic triad of fever, rash and headache is not always present when RMSF is diagnosed. It may progress to severe cases such as renal failure, disseminated intravascular coagulation and septicaemia. This report aims to present a fulminant case of RMSF associated with sepsis. It describes a female patient's case that quickly progressed to sepsis and death. The patient showed non-specific symptoms for 5 days before being admitted to a hospital. The fact that she lived in an area highly infested with Amblyomma aureolatum ticks was unknown to the medical staff until the moment she died.

Palifermin-associated papular eruption.

Science.gov (United States)

King, Brett; Knopp, Eleanor; Galan, Anjela; Nuovo, Gerard; Tigelaar, Robert; McNiff, Jennifer

2009-02-01

Palifermin is a recombinant human keratinocyte growth factor that is used to reduce the duration and severity of oral mucositis in patients undergoing hematopoietic stem cell transplantation after myelotoxic therapy. Cutaneous adverse reactions associated with keratinocyte growth factor are reported to be rash, pruritus, and erythema. After receiving palifermin following autologous hematopoietic stem cell transplantation and treatment with melphalan, a patient developed erythema and lichenoid papules that were distributed primarily in intertriginous areas. A biopsy specimen of the papules showed a striking resemblance to verrucae, but in situ hybridization studies were negative for human papillomavirus. Immunohistochemical staining with antibodies to Ki-67 and cytokeratin 5/6 showed increased keratinocyte proliferation in lesional skin. After treatment with palifermin, a papular eruption clinically resembling lichen planus or plane warts, with histologic features of verruca plana, and intertriginous erythema may occur. In this case, neither eruption required treatment, and spontaneous resolution was observed over days to weeks. Histopathologic staining patterns of Ki-67 and cytokeratin 5/6 may be useful in identifying adverse reactions to palifermin therapy.

Risk Preferences and Predictions about Others: No Association with 2D:4D Ratio

Directory of Open Access Journals (Sweden)

Katharina Lima de Miranda

2018-02-01

Full Text Available Prenatal androgen exposure affects the brain development of the fetus which may facilitate certain behaviors and decision patterns in the later life. The ratio between the lengths of second and the fourth fingers (2D:4D is a negative biomarker of the ratio between prenatal androgen and estrogen exposure and men typically have lower ratios than women. In line with the typical findings suggesting that women are more risk averse than men, several studies have also shown negative relationships between 2D:4D and risk taking although the evidence is not conclusive. Previous studies have also reported that both men and women believe women are more risk averse than men. In the current study, we re-test the relationship between 2D:4D and risk preferences in a German student sample and also investigate whether the 2D:4D ratio is associated with people’s perceptions about others’ risk preferences. Following an incentivized risk elicitation task, we asked all participants their predictions about (i others’ responses (without sex specification, (ii men’s responses, and (iii women’s responses; then measured their 2D:4D ratios. In line with the previous findings, female participants in our sample were more risk averse. While both men and women underestimated other participants’ (non sex-specific and women’s risky decisions on average, their predictions about men were accurate. We also found evidence for the false consensus effect, as risky choices are positively correlated with predictions about other participants’ risky choices. The 2D:4D ratio was not directly associated either with risk preferences or the predictions of other participants’ choices. An unexpected finding was that women with mid-range levels of 2D:4D estimated significantly larger sex differences in participants’ decisions. This finding needs further testing in future studies.

Risk Preferences and Predictions about Others: No Association with 2D:4D Ratio

Science.gov (United States)

Lima de Miranda, Katharina; Neyse, Levent; Schmidt, Ulrich

2018-01-01

Prenatal androgen exposure affects the brain development of the fetus which may facilitate certain behaviors and decision patterns in the later life. The ratio between the lengths of second and the fourth fingers (2D:4D) is a negative biomarker of the ratio between prenatal androgen and estrogen exposure and men typically have lower ratios than women. In line with the typical findings suggesting that women are more risk averse than men, several studies have also shown negative relationships between 2D:4D and risk taking although the evidence is not conclusive. Previous studies have also reported that both men and women believe women are more risk averse than men. In the current study, we re-test the relationship between 2D:4D and risk preferences in a German student sample and also investigate whether the 2D:4D ratio is associated with people’s perceptions about others’ risk preferences. Following an incentivized risk elicitation task, we asked all participants their predictions about (i) others’ responses (without sex specification), (ii) men’s responses, and (iii) women’s responses; then measured their 2D:4D ratios. In line with the previous findings, female participants in our sample were more risk averse. While both men and women underestimated other participants’ (non sex-specific) and women’s risky decisions on average, their predictions about men were accurate. We also found evidence for the false consensus effect, as risky choices are positively correlated with predictions about other participants’ risky choices. The 2D:4D ratio was not directly associated either with risk preferences or the predictions of other participants’ choices. An unexpected finding was that women with mid-range levels of 2D:4D estimated significantly larger sex differences in participants’ decisions. This finding needs further testing in future studies. PMID:29472846

Clinicopathologic review of 19 patients with systemic candidiasis with skin lesions.

Science.gov (United States)

Bae, Gee Young; Lee, Hae Woong; Chang, Sung Eun; Moon, Kee Chan; Lee, Mi Woo; Choi, Jee Ho; Koh, Jai Kyoung

2005-07-01

A diagnosis of systemic candidiasis is often delayed or missed owing to the absence of sensitive, specific, and timely diagnostic tools. Skin lesions are not common, but they can help to rapidly establish a diagnosis. We report on a 14-year experience of systemic candidiasis with skin lesions in our institution. We report the prevalence, clinical findings, histologic findings, etiologic Candida species, underlying conditions, treatment modalities, and outcomes of the cases and compare them with the previous reports. We reviewed the medical records and laboratory data of patients diagnosed with systemic candidiasis from June 1989 to September 2002 at Asan Medical Center, Seoul, Korea. We thoroughly reviewed the data on those patients with characteristic skin lesions. We included the cases in which Candida organisms were either shown or cultured from the skin. We also included the patients who had developed the characteristic rash at the onset of infection if there was no other possible explanation for the rash. Of 53 documented systemic candidiasis cases, 19 (35.8%) had the characteristic skin lesions. Fifteen patients (78.9%) had hematologic problems and were neutropenic. The skin lesions were a maculopapular or nodular rash and plaques. In addition to the trunk and proximal extremities, the rash also involved the face and distal extremities. The rashes were mostly purpuric, not consistently associated with underlying thrombocytopenia but also associated with underlying vascular damage as a result of Candida organisms. The underlying vascular damage also caused intraepidermal necrotic and vesicular change. One case of transepidermal elimination of organisms was newly found. The most common causative species was Candida tropicalis in the 19 patients with skin lesions, in contrast with Candida albicans in a total of 53 patients. The mortality rate was 84.2%. The prevalence of systemic candidiasis-associated skin lesions may be higher than previously reported

Prediction of SEP Peak Proton Intensity Based on CME Speed, Direction and Observations of Associated Solar Phenomena

Science.gov (United States)

Richardson, I. G.; Mays, M. L.; Thompson, B. J.; Kwon, R.; Frechette, B. P.

2017-12-01

We assess whether a formula obtained by Richardson et al. (Solar Phys., 289, 3059, 2014; DOI 10.1007/s11207-014-0524-8) relating the intensity of 14-24 MeV protons in a solar energetic particle event at 1 AU to the solar event location and the speed of the associated coronal mass ejection (CME), may be used to "predict" the intensity of a solar energetic particle event. Starting with a subset of several hundred CMEs in the CCMC/SWRC DONKI real-time database (http://kauai.ccmc.gsfc.nasa.gov/DONKI/) selected without consideration of whether they were associated with SEP events, we first use the CME speed and direction to predict the proton intensity at Earth or the STEREO spacecraft using this formula. Since most of these CMEs were not in fact associated with SEP events, many "false alarms" result. We then examine whether considering other phenomena which may accompany the CMEs, such as the X-ray flare intensity and the properties of type II and type III radio emissions, may help to reduce the false alarm rate. We also use CME parameters calculated from an ellipsoidal shell fit to multi-spacecraft CME shock observations for a smaller number of events to predict the SEP intensity. We calculate skill scores for each case and assess whether the Richardson et al. (2014) formula, using additional observations to reduce the false alarm rate, has any potential as a SEP prediction tool, assuming that the required observations could be acquired sufficiently rapidly following the onset of the related solar event/CME.

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study.

Science.gov (United States)

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models. Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the "best cut-off" of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as "positive outcome" are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal. Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.

Bronchiolitis obliterans organising pneumonia associated with anticonvulsant hypersensitivity syndrome induced by lamotrigine.

Science.gov (United States)

Ghandourah, Hasan; Bhandal, Samarjeet; Brundler, Marie-Anne; Noseworthy, Mary

2016-01-29

A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment. 2016 BMJ Publishing Group Ltd.

Normocomplementaemic Urticarial Vasculitis in a 19-Month-Old Girl

Directory of Open Access Journals (Sweden)

Peter Williams

2016-01-01

Full Text Available Urticaria is common in children. Urticarial vasculitis (UV is a potentially more serious, rare variant. The youngest reported case was 12 months of age. A systemically well, 19-month-old girl presented with her mother who was concerned about the development of a rash. On presentation, the child had normal vital signs, was alert, and was well and playing with toys. There was a widespread urticarial rash (raised, pruritic, and erythematous that was most apparent on the trunk with minimal rash on the legs. Overlying this urticarial rash in a similar distribution was a blotchy, palpable purpuric rash and associated hyperpigmentation. Investigations revealed a normal level of haemoglobin, white cells, platelets, and electrolytes. Renal function, international normalised ratio, and activated partial thromboplastin time were all normal. There was no blood or protein in the urine. The erythrocyte sedimentation rate was mildly elevated at 19 mm/hour. Complement results (including C1q obtained later were normal. This case is striking not only because of the rarity of UV in children but also due to the unique diagnostic and prognostic challenges that it raises.

Predicting Neural Activity Patterns Associated with Sentences Using a Neurobiologically Motivated Model of Semantic Representation.

Science.gov (United States)

Anderson, Andrew James; Binder, Jeffrey R; Fernandino, Leonardo; Humphries, Colin J; Conant, Lisa L; Aguilar, Mario; Wang, Xixi; Doko, Donias; Raizada, Rajeev D S

2017-09-01

We introduce an approach that predicts neural representations of word meanings contained in sentences then superposes these to predict neural representations of new sentences. A neurobiological semantic model based on sensory, motor, social, emotional, and cognitive attributes was used as a foundation to define semantic content. Previous studies have predominantly predicted neural patterns for isolated words, using models that lack neurobiological interpretation. Fourteen participants read 240 sentences describing everyday situations while undergoing fMRI. To connect sentence-level fMRI activation patterns to the word-level semantic model, we devised methods to decompose the fMRI data into individual words. Activation patterns associated with each attribute in the model were then estimated using multiple-regression. This enabled synthesis of activation patterns for trained and new words, which were subsequently averaged to predict new sentences. Region-of-interest analyses revealed that prediction accuracy was highest using voxels in the left temporal and inferior parietal cortex, although a broad range of regions returned statistically significant results, showing that semantic information is widely distributed across the brain. The results show how a neurobiologically motivated semantic model can decompose sentence-level fMRI data into activation features for component words, which can be recombined to predict activation patterns for new sentences. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Focal seizure associated with human parvovirus B19 infection in a non-encephalopathic child.

Science.gov (United States)

Samanta, Debopam; Willis, Erin

2016-02-01

The incidence of acute symptomatic (at the time of documented brain insult) seizures and single unprovoked seizures are 29-39 and 23-61 per 100 000 per year, respectively. After stabilization of the patient, finding the etiology of the seizure is of paramount importance. A careful history and physical examination may allow a diagnosis without need for further evaluation. In the literature, severe central nervous system involvement has been reported from human parvovirus B19 infection. We reported a previously healthy 7-year-old girl who presented after an episode of focal seizure. She was afebrile and didn't have any focal neurological abnormalities. She had erythematous malar rash along with reticulating pattern of rash over her both upper extremities. Parvovirus infection was suspected due to the characteristic erythematous malar rash. Serum human parvovirus B19 DNA polymerase chain reaction was positive which was consistent with acute parvovirus infection. Further confirmation of current infection was done with Sandwich enzyme immunoassays showing positive anti-B19 IgM Index (>1.1). IgG index was equivocal (0.9-1.1). We report an extremely rare presentation of non-febrile seizure from acute parvovirus infection in a child without encephalopathy who had an excellent recovery. Timely diagnosis can provide counselling regarding future seizure recurrence risk, curtail expenditure from expensive diagnostic work up and provide additional recommendations about potential risks to a pregnant caregiver.

The Functional Movement Screen and Injury Risk: Association and Predictive Value in Active Men.

Science.gov (United States)

Bushman, Timothy T; Grier, Tyson L; Canham-Chervak, Michelle; Anderson, Morgan K; North, William J; Jones, Bruce H

2016-02-01

The Functional Movement Screen (FMS) is a series of 7 tests used to assess the injury risk in active populations. To determine the association of the FMS with the injury risk, assess predictive values, and identify optimal cut points using 3 injury types. Cohort study; Level of evidence, 2. Physically active male soldiers aged 18 to 57 years (N = 2476) completed the FMS. Demographic and fitness data were collected by survey. Medical record data for overuse injuries, traumatic injuries, and any injury 6 months after the FMS assessment were obtained. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated along with the receiver operating characteristic (ROC) to determine the area under the curve (AUC) and identify optimal cut points for the risk assessment. Risks, risk ratios (RRs), odds ratios (ORs), and 95% CIs were calculated to assess injury risks. Soldiers who scored ≤14 were at a greater risk for injuries compared with those who scored >14 using the composite score for overuse injuries (RR, 1.84; 95% CI, 1.63-2.09), traumatic injuries (RR, 1.26; 95% CI, 1.03-1.54), and any injury (RR, 1.60; 95% CI, 1.45-1.77). When controlling for other known injury risk factors, multivariate logistic regression analysis identified poor FMS performance (OR [score ≤14/19-21], 2.00; 95% CI, 1.42-2.81) as an independent risk factor for injuries. A cut point of ≤14 registered low measures of predictive value for all 3 injury types (sensitivity, 28%-37%; PPV, 19%-52%; AUC, 54%-61%). Shifting the injury risk cut point of ≤14 to the optimal cut points indicated by the ROC did not appreciably improve sensitivity or the PPV. Although poor FMS performance was associated with a higher risk of injuries, it displayed low sensitivity, PPV, and AUC. On the basis of these findings, the use of the FMS to screen for the injury risk is not recommended in this population because of the low predictive value and misclassification of the

Short communication: high prevalence of drug resistance in HIV type 1-infected children born in Honduras and Belize 2001 to 2004.

Science.gov (United States)

Parham, Leda; de Rivera, Ivette Lorenzana; Murillo, Wendy; Naver, Lars; Largaespada, Natalia; Albert, Jan; Karlsson, Annika C

2011-10-01

Antiretroviral therapy has had a great impact on the prevention of mother-to-child transmission (MTCT) of HIV-1. However, development of drug resistance, which could be subsequently transmitted to the child, is a major concern. In Honduras and Belize the prevalence of drug resistance among HIV-1-infected children remains unknown. A total of 95 dried blood spot samples was obtained from HIV-1-infected, untreated children in Honduras and Belize born during 2001 to 2004, when preventive antiretroviral therapy was often suboptimal and consisted of monotherapy with nevirapine or zidovudine. Partial HIV-1 pol gene sequences were successfully obtained from 66 children (Honduras n=55; Belize n=11). Mutations associated with drug resistance were detected in 13% of the Honduran and 27% of the Belizean children. Most of the mutations detected in Honduras (43%) and all mutations detected in Belize were associated with resistance to nonnucleoside reverse transcriptase inhibitors, which was expected from the wide use of nevirapine to prevent MTCT during the study period. In addition, although several mothers reported that they had not received antiretroviral therapy, mutations associated with resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors were found in Honduras. This suggests prior and unreported use of these drugs, or that these women had been infected with resistant virus. The present study demonstrates, for the first time, the presence of drug resistance-associated mutations in HIV-1-infected Honduran and Belizean children.

Paired-Associate and Feedback-Based Weather Prediction Tasks Support Multiple Category Learning Systems

OpenAIRE

Li, Kaiyun; Fu, Qiufang; Sun, Xunwei; Zhou, Xiaoyan; Fu, Xiaolan

2016-01-01

It remains unclear whether probabilistic category learning in the feedback-based weather prediction task (FB-WPT) can be mediated by a non-declarative or procedural learning system. To address this issue, we compared the effects of training time and verbal working memory, which influence the declarative learning system but not the non-declarative learning system, in the FB and paired-associate (PA) WPTs, as the PA task recruits a declarative learning system. The results of Experiment 1 showed...

Predicting Aggressive Tendencies by Visual Attention Bias Associated with Hostile Emotions.

Science.gov (United States)

Lin, Ping-I; Hsieh, Cheng-Da; Juan, Chi-Hung; Hossain, Md Monir; Erickson, Craig A; Lee, Yang-Han; Su, Mu-Chun

2016-01-01

The goal of the current study is to clarify the relationship between social information processing (e.g., visual attention to cues of hostility, hostility attribution bias, and facial expression emotion labeling) and aggressive tendencies. Thirty adults were recruited in the eye-tracking study that measured various components in social information processing. Baseline aggressive tendencies were measured using the Buss-Perry Aggression Questionnaire (AQ). Visual attention towards hostile objects was measured as the proportion of eye gaze fixation duration on cues of hostility. Hostility attribution bias was measured with the rating results for emotions of characters in the images. The results show that the eye gaze duration on hostile characters was significantly inversely correlated with the AQ score and less eye contact with an angry face. The eye gaze duration on hostile object was not significantly associated with hostility attribution bias, although hostility attribution bias was significantly positively associated with the AQ score. Our findings suggest that eye gaze fixation time towards non-hostile cues may predict aggressive tendencies.

Predictive factors associated with neck pain in patients with cervical disc degeneration: A cross-sectional study focusing on Modic changes.

Science.gov (United States)

Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

2017-10-01

The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease.We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain.In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044-1.112), spondylolisthesis (OR 1.339, 95% CI 1.226-1.462), and annular tear (OR 1.188, 95% CI 1.021-1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022-2.394), spondylolisthesis (OR 1.486, 95% CI 1.082-2.041), and MCs (OR 1.152, 95% CI 1.074-1.234) were associated with PNP.We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain.

Intrinsic spontaneous brain activity predicts individual variability in associative memory in older adults.

Science.gov (United States)

Zheng, Zhiwei; Li, Rui; Xiao, Fengqiu; He, Rongqiao; Zhang, Shouzi; Li, Juan

2018-04-19

Older adults demonstrate notable individual differences in associative memory. Here, resting-state functional magnetic resonance imaging (rsfMRI) was used to investigate whether intrinsic brain activity at rest could predict individual differences in associative memory among cognitively healthy older adults. Regional amplitude of low-frequency fluctuations (ALFF) analysis and a correlation-based resting-state functional connectivity (RSFC) approach were used to analyze data acquired from 102 cognitively normal elderly who completed the paired-associative learning test (PALT) and underwent fMRI scans. Participants were divided into two groups based on the retrospective self-reports on whether or not they utilized encoding strategies during the PALT. The behavioral results revealed better associative memory performance in the participants who reported utilizing memory strategies compared with participants who reported not doing so. The fMRI results showed that higher associative memory performance was associated with greater functional connectivity between the right superior frontal gyrus and the right posterior cerebellum lobe in the strategy group. The regional ALFF values in the right superior frontal gyrus were linked to associative memory performance in the no-strategy group. These findings suggest that the regional spontaneous fluctuations and functional connectivity during rest may subserve the individual differences in the associative memory in older adults, and that this is modulated by self-initiated memory strategy use. © 2018 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in South India.

Science.gov (United States)

Saravanan, Shanmugam; Kausalya, Bagavathi; Gomathi, Selvamurthi; Sivamalar, Sathasivam; Pachamuthu, Balakrishnan; Selvamuthu, Poongulali; Pradeep, Amrose; Sunil, Solomon; Mothi, Sarvode N; Smith, Davey M; Kantor, Rami

2017-06-01

We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings. To complement these investigations, we also analyzed the sequences in Stanford database, Monogram weighted score, and DUET weighted score algorithms for ETR susceptibility and found almost perfect agreement between the three algorithms in predicting ETR susceptibility from genotypic data.

Ranking prediction model using the competition record of Ladies Professional Golf Association players.

Science.gov (United States)

Chae, Jin Seok; Park, Jin; So, Wi-Young

2017-07-28

The purpose of this study was to suggest a ranking prediction model using the competition record of the Ladies Professional Golf Association (LPGA) players. The top 100 players on the tour money list from the 2013-2016 US Open were analyzed in this model. Stepwise regression analysis was conducted to examine the effect of performance and independent variables (i.e., driving accuracy, green in regulation, putts per round, driving distance, percentage of sand saves, par-3 average, par-4 average, par-5 average, birdies average, and eagle average) on dependent variables (i.e., scoring average, official money, top-10 finishes, winning percentage, and 60-strokes average). The following prediction model was suggested:Y (Scoring average) = 55.871 - 0.947 (Birdies average) + 4.576 (Par-4 average) - 0.028 (Green in regulation) - 0.012 (Percentage of sand saves) + 2.088 (Par-3 average) - 0.026 (Driving accuracy) - 0.017 (Driving distance) + 0.085 (Putts per round)Y (Official money) = 6628736.723 + 528557.907 (Birdies average) - 1831800.821 (Par-4 average) + 11681.739 (Green in regulation) + 6476.344 (Percentage of sand saves) - 688115.074 (Par-3 average) + 7375.971 (Driving accuracy)Y (Top-10 finish%) = 204.462 + 12.562 (Birdies average) - 47.745 (Par-4 average) + 1.633 (Green in regulation) - 5.151 (Putts per round) + 0.132 (Percentage of sand saves)Y (Winning percentage) = 49.949 + 3.191 (Birdies average) - 15.023 (Par-4 average) + 0.043 (Percentage of sand saves)Y (60-strokes average) = 217.649 + 13.978 (Birdies average) - 44.855 (Par-4 average) - 22.433 (Par-3 average) + 0.16 (Green in regulation)Scoring of the above five prediction models and the prediction of golf ranking in the 2016 Women's Golf Olympic competition in Rio revealed a significant correlation between the predicted and real ranking (r = 0.689, p ranking prediction model using LPGA data may help coaches and players to identify which players are likely to participate in Olympic and World competitions, based

Trichoscopic Findings of Erosive Pustular Dermatosis of the Scalp Associated with Gefitinib

Directory of Open Access Journals (Sweden)

Tomohisa Fukui

2017-06-01

Full Text Available Alopecia associated with epidermal growth factor receptor (EGFR inhibitor therapy is a rare cutaneous side effect with the potential to progress to scarring alopecia. Thus, dermatologists should make an early diagnosis. We present the case of a 57-year-old Japanese female with scarring alopecia associated with gefitinib, which is an EGFR inhibitor, including trichoscopic findings. The patient treated with gefitinib for non-small cell lung cancer experienced skin rash and hair loss of the scalp. The scalp lesions appeared similar to erosive pustular dermatosis of the scalp. Trichoscopic examination showed follicular keratotic plugging, milky red areas, white patches, hair shaft disorder, tapering hair, and absence of follicular opening. Histological examination showed ruptured hair follicles with a perifollicular infiltration of plasma cells, lymphocytes, and histiocytes. Oral minocycline and topical steroid treatment produced no improvement. With a reduction in the gefitinib dosage, alopecia gradually improved, although scarring remained. We consider these trichoscopic findings and suspect that follicular keratotic plugging might be a finding associated with scarring alopecia due to EGFR inhibitor therapy.

A novel method of predicting microRNA-disease associations based on microRNA, disease, gene and environment factor networks.

Science.gov (United States)

Peng, Wei; Lan, Wei; Zhong, Jiancheng; Wang, Jianxin; Pan, Yi

2017-07-15

MicroRNAs have been reported to have close relationship with diseases due to their deregulation of the expression of target mRNAs. Detecting disease-related microRNAs is helpful for disease therapies. With the development of high throughput experimental techniques, a large number of microRNAs have been sequenced. However, it is still a big challenge to identify which microRNAs are related to diseases. Recently, researchers are interesting in combining multiple-biological information to identify the associations between microRNAs and diseases. In this work, we have proposed a novel method to predict the microRNA-disease associations based on four biological properties. They are microRNA, disease, gene and environment factor. Compared with previous methods, our method makes predictions not only by using the prior knowledge of associations among microRNAs, disease, environment factors and genes, but also by using the internal relationship among these biological properties. We constructed four biological networks based on the similarity of microRNAs, diseases, environment factors and genes, respectively. Then random walking was implemented on the four networks unequally. In the walking course, the associations can be inferred from the neighbors in the same networks. Meanwhile the association information can be transferred from one network to another. The results of experiment showed that our method achieved better prediction performance than other existing state-of-the-art methods. Copyright © 2017 Elsevier Inc. All rights reserved.

La Verbena azul en el tratamiento del niño con salpullido The blue Verbena to treat the child with rash

Directory of Open Access Journals (Sweden)

Roberto Galiano Piquet

2012-03-01

Full Text Available Introducción: la miliaria es una enfermedad inflamatoria de la piel, usualmente conocida como salpullido, es muy frecuente en niños pequeños sobre todo en los meses de verano. Objetivo: valorar la eficacia de la infusión de Verbena azul en el control de la miliaria común. Métodos: se realizó un ensayo clínico fase II, a partir de la preparación de una infusión de hojas frescas o secas molidas, que se vertieron en 12 litros de agua hirviente, se tapó y se separó del fuego después de añadirle la planta, se dejó reposar y se coló. Fue aplicada tibia en todo el cuerpo durante 21 días, en dos secciones, al levantarse, y en la tarde luego del baño diario. El estudio se realizó en 30 lactantes de raza blanca, que acudieron con esta patología a la consulta de Medicina Natural y Tradicional, en el consultorio 6 del poblado de Altagracia, en el periodo entre junio del 2004 y junio del 2005, los cuales pertenecían al Policlínico Comunitario Docente "Carlos J. Finlay" de la Ciudad de Camagüey. Los datos se recogieron mediante una encuesta, confeccionada de acuerdo con los objetivos planteados en la investigación. Resultados: el grupo más afectado fue el de 3 a 6 meses, todos los pacientes fueron blancos, no se encontraron diferencias significativas en cuanto al sexo. La variedad clínica más frecuente fue la cristalina, y los meses en que más se presentó fueron entre junio y agosto. Conclusiones: este tratamiento presentó una alta eficacia en el control de la sintomatología de la miliaria común; se curaron 9 de cada 10 pacientes.Introduction: miliaria is an skin inflammatory disease known as rash and is very frequent in small children mainly during summer months. Objective: assessing the efficacy of the infusion of blue Verbena in controlling common heat rash. Methods: a phase II clinical trial was conducted from the preparation of an infusion of fresh leaves or dry grinded poured out in 12 liters of boiling water, was covered

Stress and decision making: the role of impulsive personality

OpenAIRE

Wise, Richard Julian

2017-01-01

Stress, gender, and impulsive personality traits are each associated with altered decision making, but no studies have yet examined interactions between all of these factors. Impulsive personality can be parsed into five subtypes, consisting of Negative Urgency, the tendency to act rashly in the face of extreme negative emotion; Positive Urgency, the tendency to act rashly in the face of strong positive emotion; Lack of Premeditation, the tendency to insufficiently consider actions prior to t...

Prediction of the damage-associated non-synonymous single nucleotide polymorphisms in the human MC1R gene.

Science.gov (United States)

Hepp, Diego; Gonçalves, Gislene Lopes; de Freitas, Thales Renato Ochotorena

2015-01-01

The melanocortin 1 receptor (MC1R) is involved in the control of melanogenesis. Polymorphisms in this gene have been associated with variation in skin and hair color and with elevated risk for the development of melanoma. Here we used 11 computational tools based on different approaches to predict the damage-associated non-synonymous single nucleotide polymorphisms (nsSNPs) in the coding region of the human MC1R gene. Among the 92 nsSNPs arranged according to the predictions 62% were classified as damaging in more than five tools. The classification was significantly correlated with the scores of two consensus programs. Alleles associated with the red hair color (RHC) phenotype and with the risk of melanoma were examined. The R variants D84E, R142H, R151C, I155T, R160W and D294H were classified as damaging by the majority of the tools while the r variants V60L, V92M and R163Q have been predicted as neutral in most of the programs The combination of the prediction tools results in 14 nsSNPs indicated as the most damaging mutations in MC1R (L48P, R67W, H70Y, P72L, S83P, R151H, S172I, L206P, T242I, G255R, P256S, C273Y, C289R and R306H); C273Y showed to be highly damaging in SIFT, Polyphen-2, MutPred, PANTHER and PROVEAN scores. The computational analysis proved capable of identifying the potentially damaging nsSNPs in MC1R, which are candidates for further laboratory studies of the functional and pharmacological significance of the alterations in the receptor and the phenotypic outcomes.

Prediction of the damage-associated non-synonymous single nucleotide polymorphisms in the human MC1R gene.

Directory of Open Access Journals (Sweden)

Diego Hepp

Full Text Available The melanocortin 1 receptor (MC1R is involved in the control of melanogenesis. Polymorphisms in this gene have been associated with variation in skin and hair color and with elevated risk for the development of melanoma. Here we used 11 computational tools based on different approaches to predict the damage-associated non-synonymous single nucleotide polymorphisms (nsSNPs in the coding region of the human MC1R gene. Among the 92 nsSNPs arranged according to the predictions 62% were classified as damaging in more than five tools. The classification was significantly correlated with the scores of two consensus programs. Alleles associated with the red hair color (RHC phenotype and with the risk of melanoma were examined. The R variants D84E, R142H, R151C, I155T, R160W and D294H were classified as damaging by the majority of the tools while the r variants V60L, V92M and R163Q have been predicted as neutral in most of the programs The combination of the prediction tools results in 14 nsSNPs indicated as the most damaging mutations in MC1R (L48P, R67W, H70Y, P72L, S83P, R151H, S172I, L206P, T242I, G255R, P256S, C273Y, C289R and R306H; C273Y showed to be highly damaging in SIFT, Polyphen-2, MutPred, PANTHER and PROVEAN scores. The computational analysis proved capable of identifying the potentially damaging nsSNPs in MC1R, which are candidates for further laboratory studies of the functional and pharmacological significance of the alterations in the receptor and the phenotypic outcomes.

Acute generalized exanthematous pustulosis and polyarthritis associated with a novel CARD14 mutation.

Science.gov (United States)

Podlipnik, Sebastian; Castellanos-Moreira, Raul; Florez-Enrich, Helena; Arostegui, Juan Ignacio; Mascaró, José Manuel

2018-02-01

Acute generalised exanthematous pustulosis (AGEP) is a rare toxicoderma characterised by an acute onset rash, with many sterile pustules on the surface, high fever and increased acute phase reactants. We report the case of a patient who presented to the dermatology department with an AGEP and polyarthritis, in which a novel CARD14 mutation was identified. The pathophysiological mechanism of AGEP remains unclear, although mutations in the IL36RN gene have been identified in a small subset of AGEP patients. Similarly, mutations in the CARD14 gene have been linked to pustular types of psoriasis and familiar cases of pityriasis rubra pilaris; however, there are no reports associating mutations in the CARD14 gene with AGEP. © 2017 The Australasian College of Dermatologists.

Prediction of multiphase equilibria in associating fluids by a contact-site quasichemical equation of state

International Nuclear Information System (INIS)

Prikhodko, I.V.; Victorov, A.I.; Loos, Th.W.de

1995-01-01

A contract-site quasichemical equation of state has been used for the modeling of different kinds of fluid phase equilibria (between a gas phase and one or more liquids) over a wide range of conditions. Among the systems of interest are the ternary mixtures water + alkanols + hydrocarbons (alkanes or alkynes), water + alkanols (or acetone) + CO 2 , water + polyoxyethyleneglycol ethers + heavy alkanes. The model has been applied to describing the thermodynamic properties of the binary subsystems and to predict the phase behavior of the ternary systems. For longer-chain alkanols and hydrocarbons a group-contribution approach is implemented, which allows the modeling when no experimental data are available. The model gives reasonable predictions of phase behavior and the correct trends in the calculated phase diagrams in most cases. The concentrations of associates in liquid and gas phases are estimated by the model and compared with some experimental and computer simulation data. The predictive abilities of the model, its limitations, and possible ways of its improvement are discussed

Identification of risk products for fragrance contact allergy: a case-referent study based on patients' histories.

Science.gov (United States)

Johansen, J D; Andersen, T F; Kjøller, M; Veien, N; Avnstorp, C; Andersen, K E; Menné, T

1998-06-01

Fragrances are the first or second most common cause of contact allergy in dermatitis patients. The aim of this study was to identify risk products for fragrance contact allergy. The design was a case-control study with a case group of 78 fragrance-mix-positive eczema patients and two control groups, one consisting of 1,279 subjects selected as a random sample of the general population and the other consisting of 806 fragrance-mix-negative eczema patients. The identification of risk products was based on the patients' histories of rash to scented products. Analysis of the associations between first-time rash caused by different specified product categories and fragrance mix sensitivity was performed using logistic regression. It was found that first-time rash caused by deodorant sprays and/or perfumes were related to fragrance contact allergy in a comparison with both control groups. The risk (odds ratio) of being diagnosed as fragrance allergic was 2.3 to 2.9 greater in cases of a history of first-time rash to deodorant sprays and 3.3 to 3.4 greater in cases of a history of rash to perfumes than if no such history were present. First-time rash to cleansing agents, deodorant sticks, or hand lotions was also statistically significant but only in comparison with one of the control groups. Safety evaluation of fragrance materials used in perfumes and deodorant sprays should be performed with special attention.

Mycoplasma pneumoniae and atypical Stevens-Johnson syndrome: a case series.

Science.gov (United States)

Ravin, Karen A; Rappaport, Lara D; Zuckerbraun, Noel S; Wadowsky, Robert M; Wald, Ellen R; Michaels, Marian M

2007-04-01

Mycoplasma pneumoniae is a common cause of community-acquired respiratory illness in the adolescent population. Stevens-Johnson syndrome is an extrapulmonary manifestation that has been associated with M. pneumoniae infections. Three adolescent males presented within a 1-month period with M. pneumoniae respiratory illnesses and severe mucositis but without the classic rash typical of Stevens-Johnson. Diagnosis was facilitated by the use of a polymerase chain reaction-based assay. This case series highlights the potential for M. pneumoniae-associated Stevens-Johnson syndrome to occur without rash and supports the use of polymerase chain reaction for early diagnosis.

Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

International Nuclear Information System (INIS)

Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

2013-01-01

It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

Energy Technology Data Exchange (ETDEWEB)

Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

2013-08-15

It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

Risk factors associated with severe scrub typhus in Shandong, northern China

Directory of Open Access Journals (Sweden)

Luyan Zhang

2014-12-01

Conclusions: This study indicates that improved diagnosis and timely treatment are important factors for the prevention of severe scrub typhus. When scrub typhus patients present with a rash, lymphadenopathy, or blood platelet count <100 × 109/l, clinicians should be alert to the appearance of severe complications.

Development and validation of a prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults.

Science.gov (United States)

Mathioudakis, Nestoras Nicolas; Everett, Estelle; Routh, Shuvodra; Pronovost, Peter J; Yeh, Hsin-Chieh; Golden, Sherita Hill; Saria, Suchi

2018-01-01

To develop and validate a multivariable prediction model for insulin-associated hypoglycemia in non-critically ill hospitalized adults. We collected pharmacologic, demographic, laboratory, and diagnostic data from 128 657 inpatient days in which at least 1 unit of subcutaneous insulin was administered in the absence of intravenous insulin, total parenteral nutrition, or insulin pump use (index days). These data were used to develop multivariable prediction models for biochemical and clinically significant hypoglycemia (blood glucose (BG) of ≤70 mg/dL and model development and validation, respectively. Using predictors of age, weight, admitting service, insulin doses, mean BG, nadir BG, BG coefficient of variation (CV BG ), diet status, type 1 diabetes, type 2 diabetes, acute kidney injury, chronic kidney disease (CKD), liver disease, and digestive disease, our model achieved a c-statistic of 0.77 (95% CI 0.75 to 0.78), positive likelihood ratio (+LR) of 3.5 (95% CI 3.4 to 3.6) and negative likelihood ratio (-LR) of 0.32 (95% CI 0.30 to 0.35) for prediction of biochemical hypoglycemia. Using predictors of sex, weight, insulin doses, mean BG, nadir BG, CV BG , diet status, type 1 diabetes, type 2 diabetes, CKD stage, and steroid use, our model achieved a c-statistic of 0.80 (95% CI 0.78 to 0.82), +LR of 3.8 (95% CI 3.7 to 4.0) and -LR of 0.2 (95% CI 0.2 to 0.3) for prediction of clinically significant hypoglycemia. Hospitalized patients at risk of insulin-associated hypoglycemia can be identified using validated prediction models, which may support the development of real-time preventive interventions.

Group spike-and-slab lasso generalized linear models for disease prediction and associated genes detection by incorporating pathway information.

Science.gov (United States)

Tang, Zaixiang; Shen, Yueping; Li, Yan; Zhang, Xinyan; Wen, Jia; Qian, Chen'ao; Zhuang, Wenzhuo; Shi, Xinghua; Yi, Nengjun

2018-03-15

Large-scale molecular data have been increasingly used as an important resource for prognostic prediction of diseases and detection of associated genes. However, standard approaches for omics data analysis ignore the group structure among genes encoded in functional relationships or pathway information. We propose new Bayesian hierarchical generalized linear models, called group spike-and-slab lasso GLMs, for predicting disease outcomes and detecting associated genes by incorporating large-scale molecular data and group structures. The proposed model employs a mixture double-exponential prior for coefficients that induces self-adaptive shrinkage amount on different coefficients. The group information is incorporated into the model by setting group-specific parameters. We have developed a fast and stable deterministic algorithm to fit the proposed hierarchal GLMs, which can perform variable selection within groups. We assess the performance of the proposed method on several simulated scenarios, by varying the overlap among groups, group size, number of non-null groups, and the correlation within group. Compared with existing methods, the proposed method provides not only more accurate estimates of the parameters but also better prediction. We further demonstrate the application of the proposed procedure on three cancer datasets by utilizing pathway structures of genes. Our results show that the proposed method generates powerful models for predicting disease outcomes and detecting associated genes. The methods have been implemented in a freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). nyi@uab.edu. Supplementary data are available at Bioinformatics online.

Bullous Henoch–Schonlein purpura with involvement of face

Directory of Open Access Journals (Sweden)

Devdeep Mukherjee

2017-01-01

Full Text Available Henoch–Schonlein purpura (HSP with facial involvement with bullous rashes are extremely rare. A 12-year-old boy presented with abdominal pain and features of arthritis. He also had multiple purpuric rashes over his lower limbs. Gradually, he developed bullous rashes which were seen on his legs and hands and progressed to involve the face. He was confirmed to be suffering from HSP from clinical presentation and skin biopsy. The child responded well to oral steroids. Bullous lesions may be seen in HSP. However, there is neither prognostic significance of this nor does it alter the management. Other causes of bullous lesions should be ruled out. As facial involvement is associated with renal and gastrointestinal involvement, these children should be monitored for sequelae.

Predictive Factors Associated with Solar Energy Development in Laikipia District Central Kenya

Directory of Open Access Journals (Sweden)

Oscar Wambuguh

2015-10-01

Full Text Available The abundance of sunlight and the availability affordable solar technologies in many areas far from grid-based electricity has sparked the development of renewable energy technologies (RETs which tap solar radiation energy to provide electricity. A study on solar photovoltaics (SPVs use and utilization took place in the Wiyumiririe Location of Kenya. A purposive randomized convenience sample of 246 households was selected and landowner interviews conducted guided by a questionnaire, followed by field surveys and observations. Although solar energy contributed less than a quarter of total household energy needs, residents specifically associated it with specific developmental initiatives. Correlation and logistic regression model analyses showed that solar power development was closely associated (and thus can be predicted from five main independent variables. The findings of the study allowed the development of a probabilistic model general enough to be applicable elsewhere in the development of alternative energy resources particularly those based on solar input.

First Aid: Rashes

Science.gov (United States)

... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... avoid sunburn . If your child tends to get eczema flare-ups, avoid harsh soaps. Reviewed by: Steven ...

Predicting the Texas Windstorm Insurance Association claim payout of commercial buildings from Hurricane Ike

Science.gov (United States)

Kim, J. M.; Woods, P. K.; Park, Y. J.; Son, K.

2013-08-01

Following growing public awareness of the danger from hurricanes and tremendous demands for analysis of loss, many researchers have conducted studies to develop hurricane damage analysis methods. Although researchers have identified the significant indicators, there currently is no comprehensive research for identifying the relationship among the vulnerabilities, natural disasters, and economic losses associated with individual buildings. To address this lack of research, this study will identify vulnerabilities and hurricane indicators, develop metrics to measure the influence of economic losses from hurricanes, and visualize the spatial distribution of vulnerability to evaluate overall hurricane damage. This paper has utilized the Geographic Information System to facilitate collecting and managing data, and has combined vulnerability factors to assess the financial losses suffered by Texas coastal counties. A multiple linear regression method has been applied to develop hurricane economic damage predicting models. To reflect the pecuniary loss, insured loss payment was used as the dependent variable to predict the actual financial damage. Geographical vulnerability indicators, built environment vulnerability indicators, and hurricane indicators were all used as independent variables. Accordingly, the models and findings may possibly provide vital references for government agencies, emergency planners, and insurance companies hoping to predict hurricane damage.

Predicting Ideological Prejudice.

Science.gov (United States)

Brandt, Mark J

2017-06-01

A major shortcoming of current models of ideological prejudice is that although they can anticipate the direction of the association between participants' ideology and their prejudice against a range of target groups, they cannot predict the size of this association. I developed and tested models that can make specific size predictions for this association. A quantitative model that used the perceived ideology of the target group as the primary predictor of the ideology-prejudice relationship was developed with a representative sample of Americans ( N = 4,940) and tested against models using the perceived status of and choice to belong to the target group as predictors. In four studies (total N = 2,093), ideology-prejudice associations were estimated, and these observed estimates were compared with the models' predictions. The model that was based only on perceived ideology was the most parsimonious with the smallest errors.

Association of TLL1 Gene Polymorphism (rs1503298, T > C) with Coronary Heart Disease in PREDICT, UDACS and ED Cohorts

International Nuclear Information System (INIS)

Zain, M.; Cooper, J. A.; Li, K. W.; Palmen, J.; Acharya, J.; Howard, P.; Ireland, H.; Humphries, S. E.; Awan, F. R.; Baig, S. M.; Elkeles, R. S.

2014-01-01

Objective: To determine the sequence variant of TLL1 gene (rs1503298, T > C) in three British cohorts (PREDICT, UDACS and ED) of patients with type-2 Diabetes mellitus (T2DM) in order to assess its association with coronary heart disease (CHD). Study Design: Analytical study. Place and Duration of Study: UCL, London, UK. Participants were genotyped in 2011-2012 for TLL1 SNP. Samples and related information were previously collected in 2001-2003 for PREDICT, and in 2001-2002 for UDACS and ED groups. Methodology: Patients included in PREDICT (n=600), UDACS (n=1020) and ED (n=1240) had Diabetes. TLL1 SNP (rs1503298, T > C) was genotyped using TaqMan technology. Allele frequencies were compared using c2 test, and tested for Hardy-Weinberg equilibrium. The risk of disease was assessed from Odds ratios (OR) with 95% Confidence Intervals (95% CI). Moreover, for the PREDICT cohort, the SNP association was tested with Coronary Artery Calcification (CAC) scores. Results: No significant association was found for this SNP with CHD or CAC scores in these cohorts. Conclusion: This SNP could not be confirmed as a risk factor for CHD in T2DM patients. However, the low power of the small sample size available is a limitation to the modest effect on risk. Further studies in larger samples would be useful. (author)

Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities.

Science.gov (United States)

Lapek, John D; Greninger, Patricia; Morris, Robert; Amzallag, Arnaud; Pruteanu-Malinici, Iulian; Benes, Cyril H; Haas, Wilhelm

2017-10-01

The formation of protein complexes and the co-regulation of the cellular concentrations of proteins are essential mechanisms for cellular signaling and for maintaining homeostasis. Here we use isobaric-labeling multiplexed proteomics to analyze protein co-regulation and show that this allows the identification of protein-protein associations with high accuracy. We apply this 'interactome mapping by high-throughput quantitative proteome analysis' (IMAHP) method to a panel of 41 breast cancer cell lines and show that deviations of the observed protein co-regulations in specific cell lines from the consensus network affects cellular fitness. Furthermore, these aberrant interactions serve as biomarkers that predict the drug sensitivity of cell lines in screens across 195 drugs. We expect that IMAHP can be broadly used to gain insight into how changing landscapes of protein-protein associations affect the phenotype of biological systems.

Emotionally laden impulsivity interacts with affect in predicting addictive use of online sexual activity in men.

Science.gov (United States)

Wéry, Aline; Deleuze, Jory; Canale, Natale; Billieux, Joël

2018-01-01

The interest in studying addictive use of online sexual activities (OSA) has grown sharply over the last decade. Despite the burgeoning number of studies conceptualizing the excessive use of OSA as an addictive disorder, few have tested its relations to impulsivity, which is known to constitute a hallmark of addictive behaviors. To address this missing gap in the literature, we tested the relationships between addictive OSA use, impulsivity traits, and affect among a convenience sample of men (N=182; age, M=29.17, SD = 9.34), building upon a theoretically driven model that distinguishes the various facets of impulsivity. Results showed that negative urgency (an impulsivity trait reflecting the tendency to act rashly in negative emotional states) and negative affect interact in predicting addictive OSA use. These results highlight the pivotal role played by negative urgency and negative affect in addictive OSA use, supporting the relevance of psychological interventions that focus on improving emotional regulation (e.g., to reduce negative affect and learn healthier coping strategies) to mitigate excessive use of OSA. Copyright © 2017 Elsevier Inc. All rights reserved.

Solitary Alcohol Use in Teens Is Associated With Drinking in Response to Negative Affect and Predicts Alcohol Problems in Young Adulthood.

Science.gov (United States)

Creswell, Kasey G; Chung, Tammy; Clark, Duncan B; Martin, Christopher S

2014-09-01

Adolescent solitary drinking may represent an informative divergence from normative behavior, with important implications for understanding risk for alcohol-use disorders later in life. Within a self-medication framework, we hypothesized that solitary alcohol use would be associated with drinking in response to negative affect and that such a pattern of drinking would predict alcohol problems in young adulthood. We tested these predictions in a longitudinal study in which we examined whether solitary drinking in adolescence (ages 12-18) predicted alcohol-use disorders in young adulthood (age 25) in 466 alcohol-using teens recruited from clinical programs and 243 alcohol-using teens recruited from the community. Findings showed that solitary drinking was associated with drinking in response to negative affect during adolescence and predicted alcohol problems in young adulthood. Results indicate that drinking alone is an important type of alcohol-use behavior that increases risk for the escalation of alcohol use and the development of alcohol problems.

Homology modeling and in silico prediction of Ulcerative colitis associated polymorphisms of NOD1.

Science.gov (United States)

Majumdar, Ishani; Nagpal, Isha; Paul, Jaishree

2017-10-01

Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1. ADP binding amino acids within the nucleotide binding domain (NBD) of NOD1 were also predicted. Key residues in inter-domain interaction were identified by sequence comparison with Oryctolagus cuniculus NOD2, a related protein. Interactions between NBD and winged helix domain (WHD) were found to be conserved in NOD1. Functional and structural effect of single nucleotide polymorphisms within the NOD1 NBD domain associated with susceptibility risk to Ulcerative colitis (UC), an inflammatory disorder of the colon was evaluated by in silico studies. Mutations W219R and L349P were predicted to be damaging and disease associated by prediction programs SIFT, PolyPhen2, PANTHER, SNP&GO, PhD SNP and SNAP2. We further validated the effect of W219R and L349P mutation on NOD1 function in vitro. Elevated mRNA expression of pro-inflammatory cytokines IL8 and IL-1β was seen as compared to the wild type NOD1 in intestinal epithelial cell line HT29 when stimulated with NOD1 ligand. Thus, these mutations may indeed have a bearing on pathogenesis of inflammation during UC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer.

Science.gov (United States)

Qin, Na; Yang, Xinjie; Zhang, Quan; Li, Xi; Zhang, Hui; Lv, Jialin; Wu, Yuhua; Wang, Jinghui; Zhang, Shucai

2014-05-01

To evaluate the efficacy and safety of Icotinib - an orally administered, highly potent selective inhibitor of epidermal growth factor receptor (EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). A total of 101 patients with stage IIIb/IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival (PFS) was collected. The overall response rate (ORR) and disease control rate (DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender (P= 0.048, 95% confidence interval [CI] 1.010-6.016) and occurrence of rash (P= 0.002, 95% CI 1.667-9.809) were the independent predictive factors for ORR, while a performance status (PS) score of 0-1 (P= 0.001, 95% CI 0.024-0.402) and rash (P= 0.042, 95% CI 1.089-76.557) were the independent predictive factors for DCR. In addition, PS scores of 0-1 (P Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Treatment of stage IIIb/IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation.

Genome-wide association study, genomic prediction and marker-assisted selection for seed weight in soybean (Glycine max).

Science.gov (United States)

Zhang, Jiaoping; Song, Qijian; Cregan, Perry B; Jiang, Guo-Liang

2016-01-01

Twenty-two loci for soybean SW and candidate genes conditioning seed development were identified; and prediction accuracies of GS and MAS were estimated through cross-validation and validation with unrelated populations. Soybean (Glycine max) is a major crop for plant protein and oil production, and seed weight (SW) is important for yield and quality in food/vegetable uses of soybean. However, our knowledge of genes controlling SW remains limited. To better understand the molecular mechanism underlying the trait and explore marker-based breeding approaches, we conducted a genome-wide association study in a population of 309 soybean germplasm accessions using 31,045 single nucleotide polymorphisms (SNPs), and estimated the prediction accuracy of genomic selection (GS) and marker-assisted selection (MAS) for SW. Twenty-two loci of minor effect associated with SW were identified, including hotspots on Gm04 and Gm19. The mixed model containing these loci explained 83.4% of phenotypic variation. Candidate genes with Arabidopsis orthologs conditioning SW were also proposed. The prediction accuracies of GS and MAS by cross-validation were 0.75-0.87 and 0.62-0.75, respectively, depending on the number of SNPs used and the size of training population. GS also outperformed MAS when the validation was performed using unrelated panels across a wide range of maturities, with an average prediction accuracy of 0.74 versus 0.53. This study convincingly demonstrated that soybean SW is controlled by numerous minor-effect loci. It greatly enhances our understanding of the genetic basis of SW in soybean and facilitates the identification of genes controlling the trait. It also suggests that GS holds promise for accelerating soybean breeding progress. The results are helpful for genetic improvement and genomic prediction of yield in soybean.

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

Science.gov (United States)

Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-05-26

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

Directory of Open Access Journals (Sweden)

Nathan Erdmann

2015-08-01

Full Text Available Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1 exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE or its non-adapted (NAE version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001. However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001. CD4+ T cell responses in patients with acute HIV infection (AHI demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution.

What Money Can't Buy: Different Patterns in Decision Making About Sex and Money Predict Past Sexual Coercion Perpetration.

Science.gov (United States)

Carrier Emond, Fannie; Gagnon, Jean; Nolet, Kevin; Cyr, Gaëlle; Rouleau, Joanne-Lucine

2018-02-01

Self-reported impulsivity has been found to predict the perpetration of sexual coercion in both sexual offenders and male college students. Impulsivity can be conceptualized as a generalized lack of self-control (i.e., general perspective) or as a multifaceted construct that can vary from one context to the other (i.e., domain-specific perspective). Delay discounting, the tendency to prefer sooner smaller rewards over larger delayed rewards, is a measure of impulsive decision making. Recent sexual adaptations of delay discounting tasks can be used to test domain-specific assumptions. The present study used the UPPS-P impulsivity questionnaire, a standard money discounting task, and a sexual discounting task to predict past use of sexual coercion in a sample of 98 male college students. Results indicated that higher negative urgency scores, less impulsive money discounting, and more impulsive sexual discounting all predicted sexual coercion. Consistent with previous studies, sexuality was discounted more steeply than money by both perpetrators and non-perpetrators of sexual coercion, but this difference was twice as large in perpetrators compared to non-perpetrators. Our study identified three different predictors of sexual coercion in male college students: a broad tendency to act rashly under negative emotions, a specific difficulty to postpone sexual gratification, and a pattern of optimal non-sexual decision making. Results highlight the importance of using multiple measures, including sexuality-specific measures, to get a clear portrait of the links between impulsivity and sexual coercion.

Long-term associative learning predicts verbal short-term memory performance.

Science.gov (United States)

Jones, Gary; Macken, Bill

2018-02-01

Studies using tests such as digit span and nonword repetition have implicated short-term memory across a range of developmental domains. Such tests ostensibly assess specialized processes for the short-term manipulation and maintenance of information that are often argued to enable long-term learning. However, there is considerable evidence for an influence of long-term linguistic learning on performance in short-term memory tasks that brings into question the role of a specialized short-term memory system separate from long-term knowledge. Using natural language corpora, we show experimentally and computationally that performance on three widely used measures of short-term memory (digit span, nonword repetition, and sentence recall) can be predicted from simple associative learning operating on the linguistic environment to which a typical child may have been exposed. The findings support the broad view that short-term verbal memory performance reflects the application of long-term language knowledge to the experimental setting.

Prognosis of patients with whiplash-associated disorders consulting physiotherapy: development of a predictive model for recovery

Directory of Open Access Journals (Sweden)

Bohman Tony

2012-12-01

Full Text Available Abstract Background Patients with whiplash-associated disorders (WAD have a generally favourable prognosis, yet some develop longstanding pain and disability. Predicting who will recover from WAD shortly after a traffic collision is very challenging for health care providers such as physical therapists. Therefore, we aimed to develop a prediction model for the recovery of WAD in a cohort of patients who consulted physical therapists within six weeks after the injury. Methods Our cohort included 680 adult patients with WAD who were injured in Saskatchewan, Canada, between 1997 and 1999. All patients had consulted a physical therapist as a result of the injury. Baseline prognostic factors were collected from an injury questionnaire administered by Saskatchewan Government Insurance. The outcome, global self-perceived recovery, was assessed by telephone interviews six weeks, three and six months later. Twenty-five possible baseline prognostic factors were considered in the analyses. A prediction model was built using Cox regression. The predictive ability of the model was estimated with concordance statistics (c-index. Internal validity was checked using bootstrapping. Results Our final prediction model included: age, number of days to reporting the collision, neck pain intensity, low back pain intensity, pain other than neck and back pain, headache before collision and recovery expectations. The model had an acceptable level of predictive ability with a c-index of 0.68 (95% CI: 0.65, 0.71. Internal validation showed that our model was robust and had a good fit. Conclusions We developed a model predicting recovery from WAD, in a cohort of patients who consulted physical therapists. Our model has adequate predictive ability. However, to be fully incorporated in clinical practice the model needs to be validated in other populations and tested in clinical settings.

Prognosis of patients with whiplash-associated disorders consulting physiotherapy: development of a predictive model for recovery

Science.gov (United States)

2012-01-01

Background Patients with whiplash-associated disorders (WAD) have a generally favourable prognosis, yet some develop longstanding pain and disability. Predicting who will recover from WAD shortly after a traffic collision is very challenging for health care providers such as physical therapists. Therefore, we aimed to develop a prediction model for the recovery of WAD in a cohort of patients who consulted physical therapists within six weeks after the injury. Methods Our cohort included 680 adult patients with WAD who were injured in Saskatchewan, Canada, between 1997 and 1999. All patients had consulted a physical therapist as a result of the injury. Baseline prognostic factors were collected from an injury questionnaire administered by Saskatchewan Government Insurance. The outcome, global self-perceived recovery, was assessed by telephone interviews six weeks, three and six months later. Twenty-five possible baseline prognostic factors were considered in the analyses. A prediction model was built using Cox regression. The predictive ability of the model was estimated with concordance statistics (c-index). Internal validity was checked using bootstrapping. Results Our final prediction model included: age, number of days to reporting the collision, neck pain intensity, low back pain intensity, pain other than neck and back pain, headache before collision and recovery expectations. The model had an acceptable level of predictive ability with a c-index of 0.68 (95% CI: 0.65, 0.71). Internal validation showed that our model was robust and had a good fit. Conclusions We developed a model predicting recovery from WAD, in a cohort of patients who consulted physical therapists. Our model has adequate predictive ability. However, to be fully incorporated in clinical practice the model needs to be validated in other populations and tested in clinical settings. PMID:23273330

How not to miss autoinflammatory diseases masquerading as urticaria

DEFF Research Database (Denmark)

Krause, K; Grattan, C E; Bindslev-Jensen, C

2012-01-01

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash...... symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications...... such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss...

Psoriasis and associated variables in classification and outcome of juvenile idiopathic arthritis - an eight-year follow-up study

DEFF Research Database (Denmark)

Ekelund, Maria; Aalto, Kristiina; Fasth, Anders

2017-01-01

BACKGROUND: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA). METHODS: In all, 440 children with JIA were followed for a median of 8 years...... in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission. RESULTS: Clinical...... findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we...

Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

Directory of Open Access Journals (Sweden)

Amit C. Achhra

2012-01-01

Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

High peer popularity longitudinally predicts adolescent health risk behavior, or does it?: an examination of linear and quadratic associations.

Science.gov (United States)

Prinstein, Mitchell J; Choukas-Bradley, Sophia C; Helms, Sarah W; Brechwald, Whitney A; Rancourt, Diana

2011-10-01

In contrast to prior work, recent theory suggests that high, not low, levels of adolescent peer popularity may be associated with health risk behavior. This study examined (a) whether popularity may be uniquely associated with cigarette use, marijuana use, and sexual risk behavior, beyond the predictive effects of aggression; (b) whether the longitudinal association between popularity and health risk behavior may be curvilinear; and (c) gender moderation. A total of 336 adolescents, initially in 10-11th grades, reported cigarette use, marijuana use, and number of sexual intercourse partners at two time points 18 months apart. Sociometric peer nominations were used to examine popularity and aggression. Longitudinal quadratic effects and gender moderation suggest that both high and low levels of popularity predict some, but not all, health risk behaviors. New theoretical models can be useful for understanding the complex manner in which health risk behaviors may be reinforced within the peer context.

Association of pol diversity with antiretroviral treatment outcomes among HIV-infected African children.

Directory of Open Access Journals (Sweden)

Iris Chen

Full Text Available In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART. We measured HIV diversity in African children (ages 6-36 months enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial. Children in this cohort were exposed to single dose nevirapine (sdNVP at birth.HIV diversity was measured retrospectively using a high resolution melting (HRM diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag, one in pol, and three in env. A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions.In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity in pol (P = 0.005 and with higher mean (P = 0.014 and median (P<0.001 HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre-treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016 and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P<0.001 for all measures.In this cohort of sdNVP-exposed, ART-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.

Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development

Directory of Open Access Journals (Sweden)

Christian Hellmuth

2017-04-01

Full Text Available Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA, polar lipids, non-esterified fatty acids (NEFA, and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

Biases in attention, interpretation, memory, and associations in children with varying levels of spider fear: Inter-relations and prediction of behavior.

Science.gov (United States)

Klein, Anke M; van Niekerk, Rianne; Ten Brink, Giovanni; Rapee, Ronald M; Hudson, Jennifer L; Bögels, Susan M; Becker, Eni S; Rinck, Mike

2017-03-01

Cognitive theories suggest that cognitive biases may be related and together influence the anxiety response. However, little is known about the interrelations of cognitive bias tasks and whether they allow for an improved prediction of fear-related behavior in addition to self-reports. This study simultaneously addressed several types of cognitive biases in children, to investigate attention bias, interpretation bias, memory bias and fear-related associations, their interrelations and the prediction of behavior. Eighty-one children varying in their levels of spider fear completed the Spider Anxiety and Disgust Screening for Children and performed two Emotional Stroop tasks, a Free Recall task, an interpretation task including size and distance indication, an Affective Priming Task, and a Behavioral Assessment Test. We found an attention bias, interpretation bias, and fear-related associations, but no evidence for a memory bias. The biases showed little overlap. Attention bias, interpretation bias, and fear-related associations predicted unique variance in avoidance of spiders. Interpretation bias and fear-related associations remained significant predictors, even when self-reported fear was included as a predictor. Children were not seeking help for their spider fear and were not tested on clinical levels of spider phobia. This is the first study to find evidence that different cognitive biases each predict unique variance in avoidance behavior. Furthermore, it is also the first study in which we found evidence for a relation between fear of spiders and size and distance indication. We showed that this bias is distinct from other cognitive biases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Probability-based collaborative filtering model for predicting gene–disease associations

OpenAIRE

Zeng, Xiangxiang; Ding, Ningxiang; Rodríguez-Patón, Alfonso; Zou, Quan

2017-01-01

Background Accurately predicting pathogenic human genes has been challenging in recent research. Considering extensive gene–disease data verified by biological experiments, we can apply computational methods to perform accurate predictions with reduced time and expenses. Methods We propose a probability-based collaborative filtering model (PCFM) to predict pathogenic human genes. Several kinds of data sets, containing data of humans and data of other nonhuman species, are integrated in our mo...

Influence of Feature Encoding and Choice of Classifier on Disease Risk Prediction in Genome-Wide Association Studies.

Directory of Open Access Journals (Sweden)

Florian Mittag

Full Text Available Various attempts have been made to predict the individual disease risk based on genotype data from genome-wide association studies (GWAS. However, most studies only investigated one or two classification algorithms and feature encoding schemes. In this study, we applied seven different classification algorithms on GWAS case-control data sets for seven different diseases to create models for disease risk prediction. Further, we used three different encoding schemes for the genotypes of single nucleotide polymorphisms (SNPs and investigated their influence on the predictive performance of these models. Our study suggests that an additive encoding of the SNP data should be the preferred encoding scheme, as it proved to yield the best predictive performances for all algorithms and data sets. Furthermore, our results showed that the differences between most state-of-the-art classification algorithms are not statistically significant. Consequently, we recommend to prefer algorithms with simple models like the linear support vector machine (SVM as they allow for better subsequent interpretation without significant loss of accuracy.

Crimean-Congo Haemorrhagic Fever

Science.gov (United States)

... heart rate), lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by bleeding into the ... heart rate), lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by bleeding into the ...

Subjective fear, interference by threat, and fear associations independently predict fear-related behavior in children.

Science.gov (United States)

Klein, Anke M; Kleinherenbrink, Annelies V; Simons, Carlijn; de Gier, Erwin; Klein, Steven; Allart, Esther; Bögels, Susan M; Becker, Eni S; Rinck, Mike

2012-09-01

Several information-processing models highlight the independent roles of controlled and automatic processes in explaining fearful behavior. Therefore, we investigated whether direct measures of controlled processes and indirect measures of automatic processes predict unique variance components of children's spider fear-related behavior. Seventy-seven children between 8 and 13 years performed an Affective Priming Task (APT) measuring associative bias, a pictorial version of the Emotional Stroop Task (EST) measuring attentional bias, filled out the Spider Anxiety and Disgust Screening for Children (SADS-C) in order to assess self-perceived fear, and took part in a Behavioral Assessment Test (BAT) to measure avoidance of spiders. The SADS-C, EST, and APT did not correlate with each other. Spider fear-related behavior was best explained by SADS-C, APT, and EST together; they explained 51% of the variance in BAT behavior. No children with clinical levels of spider phobia were tested. The direct and the different indirect measures did no correlate with each other. These results indicate that both direct and indirect measures are useful for predicting unique variance components of fear-related behavior in children. The lack of relations between direct and indirect measures may explain why some earlier studies did not find stronger color-naming interference or stronger fear associations in children with high levels of self-reported fear. It also suggests that children with high levels of spider-fearful behavior have different fear-related associations and display higher interference by spider stimuli than children with non-fearful behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improvement of bottom-quark associated Higgs-boson production predictions for LHC using HERA data

Energy Technology Data Exchange (ETDEWEB)

Andrii, Gizhko; Achim, Geiser [Deutsches Elektronen-Synchrotron, Hamburg (Germany)

2016-07-01

The dependence of the inclusive total cross section of the bottom-quark associated Higgs-boson production predictions at the LHC, pp → (b anti b)H+X on the treatment of the beauty quark mass is studied in the context of CMS measurements. For two different schemes (four flavour scheme (4FS) and five flavour scheme (5FS)) the theoretical uncertainty due to the beauty quark mass is estimated, and the potential improvement arising from a QCD analysis of HERA beauty data is demonstrated.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

Science.gov (United States)

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-12-01

♦ As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction.

Science.gov (United States)

Sutherland, Scott M

2018-06-09

Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to nephrotoxins accounts for 15-25% of AKI. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Characterization of DNAPL Source Zone Architecture and Prediction of Associated Plume Response: Progress and Perspectives

Science.gov (United States)

Abriola, L. M.; Pennell, K. D.; Ramsburg, C. A.; Miller, E. L.; Christ, J.; Capiro, N. L.; Mendoza-Sanchez, I.; Boroumand, A.; Ervin, R. E.; Walker, D. I.; Zhang, H.

2012-12-01

It is now widely recognized that the distribution of contaminant mass will control both the evolution of aqueous phase plumes and the effectiveness of many source zone remediation technologies at sites contaminated by dense nonaqueous phase liquids (DNAPLs). Advances in the management of sites containing DNAPL source zones, however, are currently hampered by the difficulty associated with characterizing subsurface DNAPL 'architecture'. This presentation provides an overview of recent research, integrating experimental and mathematical modeling studies, designed to improve our ability to characterize DNAPL distributions and predict associated plume response. Here emphasis is placed on estimation of the most information-rich DNAPL architecture metrics, through a combination of localized in situ tests and more readily available plume transect concentration observations. Estimated metrics will then serve as inputs to an upscaled screening model for prediction of long term plume response. Machine learning techniques were developed and refined to identify a variety of source zone metrics and associated confidence intervals through the processing of down gradient concentration data. Estimated metrics include the volumes and volume percentages of DNAPL in pools and ganglia, as well as their ratio (pool fraction). Multiphase flow and transport simulations provided training data for model development and assessment that are representative of field-scale DNAPL source zones and their evolving plumes. Here, a variety of release and site heterogeneity (sequential Gaussian permeability) conditions were investigated. Push-pull tracer tests were also explored as a means to provide localized in situ observations to refine these metric estimates. Here, two-dimensional aquifer cell experiments and mathematical modeling were used to quantify upscaled interphase mass transfer rates and the interplay between injection and extraction rates, local source zone architecture, and tracer

A cross-sectional study of the magnitude, barriers, and outcomes of HIV status disclosure among women participating in a perinatal HIV transmission study, "the Nevirapine Repeat Pregnancy study".

Science.gov (United States)

Kiweewa, Flavia M; Bakaki, Paul M; McConnell, Michelle S; Musisi, Maria; Namirembe, Constance; Nakayiwa, Frances; Kusasira, Fiona; Nakintu, Dorothy; Mubiru, Michael C; Musoke, Philippa; Fowler, Mary Glenn

2015-09-29

HIV status disclosure is a difficult emotional task for HIV-infected persons and may create the opportunity for both social support and rejection. In this study, we evaluated the proportions, patterns, barriers and outcomes of HIV- 1 status disclosure among a group of women in Uganda. An exit interview was conducted one year post-partum for 85 HIV-infected women who participated in a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naïve women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere University-Johns Hopkins University Research Collaboration, Kampala-Uganda, between June 2004 and June 2006. Of the 85 women interviewed, 99 % had disclosed their HIV status to at least one other person. Disclosure proportions ranged between 1 % to employer(s) and 69 % to a relative other than a parent. Only 38 % of the women had disclosed to their sex partners. Women with an HIV-infected baby were more likely than those with an uninfected baby to disclose to their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to disclose to a partner if they had previously disclosed to another relative than if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non-disclosure included fear of separation from the partner and subsequent loss of financial support 34 %, and not living with the partner (not having opportunities to disclose) 26 %. While most women (67 %) reported getting social support following disclosure, 22 % reported negative outcomes (neglect, separation from their partners, and loss of financial support). Following disclosure of HIV status, 9 % of women reported that their partner (s) decided to have an HIV test. Results from this study show high overall HIV disclosure proportions and how this disclosure of HIV status can foster social support. However, proportions of disclosure specifically to male sex partners were low, which suggests the need for interventions aimed at increasing male

Mathematical model for prediction of droplet sizes and distribution associated with impact of liquid-containing projectile

International Nuclear Information System (INIS)

Shelke, Ashish V.; Gera, B.; Maheshwari, N.K.; Singh, R.K.

2018-01-01

After the events of 9/11, the impact of fast flying commercial aircraft is considered as major hazard threatening the Nuclear Power Plant's (NPP) safety. The study of fuel spillage phenomenon and fireball formation is important to understand fire hazards due to burning of dispersed aviation fuel. The detailed analysis of fuel dispersion is very difficult to deliberate because both, large NPP structures and the large size of commercial aircrafts. Sandia National Laboratories, USA conducted impact tests using cylindrical projectiles filled with water to measure the associated parameters. Due to combustion properties and volatile nature of hydrocarbon fuels, the obtained parameters from impact studies using water are incomplete in fire analysis of flammable droplet clouds. A mathematical model is developed for prediction of droplet sizes and distribution associated with the impact of a liquid-containing projectile. The model can predict the transient behavior of droplet cloud. It is validated with experimental data available in literature. In the present study, the analysis has been performed using water and kerosene. The data obtained can be utilized as boundary and initial condition for CFD analysis. This information is useful for fire hazard analysis of aircraft impacts on NPP structures.

Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study.

Science.gov (United States)

Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; Sarriff, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

2015-09-30

The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period of six years (2008 - 2013) was performed. Patient's demographics, clinical and laboratory findings were recorded via structured data collection form. Patients were categorized into dengue fever (DF) and dengue hemorrhagic fever (DHF). Appropriate statistical methods were used to compare these two groups in order to determine difference in clinico-laboratory characteristics and to identify independent risk factors of DHF. A total 667 dengue patients (30.69 ± 16.13 years; Male: 56.7 %) were reviewed. Typical manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting, abdominal pain and skin rash were observed in more than 40 % patients. DHF was observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath, pleural effusion and thick gall bladder were more significantly (P  40 years (OR: 4.1, P hospitalization (OR: 2.3, P = 0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our study. Current study demonstrated that DF and DHF present significantly different clinico-laboratory profile. Older age, secondary infection, diabetes mellitus, lethargy, thick gallbladder and delayed hospitalization significantly predict DHF. Prior knowledge of expected clinical profile and predictors of DHF/DSS development would provide information to identify individuals at higher risk and on the other hand, give sufficient time to clinicians for reducing dengue related morbidity and mortality.

External Validation of the ISAN, A2DS2, and AIS-APS Scores for Predicting Stroke-Associated Pneumonia.

Science.gov (United States)

Zapata-Arriaza, Elena; Moniche, Francisco; Blanca, Pardo-Galiana; Bustamante, Alejandro; Escudero-Martínez, Irene; Uclés, Oscar; Ollero-Ortiz, Ángela; Sánchez-García, Jose Antonio; Gamero, Miguel Ángel; Quesada, Ángeles; Vidal De Francisco, Diana; Romera, Mercedes; De la Cruz, Carlos; Sanz, Gema; Montaner, Joan

2018-03-01

The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN), Age, Atrial Fibrillation, Dysphagia, male sex, and National Institutes of Health Stroke Scale (A2DS2), and acute ischemic stroke-associated pneumonia score (AIS-APS) scores were created to predict stroke-associated pneumonia (SAP), one of the most important medical stroke complications. External validation of all such scores in an acute stroke population was the aim of our study. Patients with ischemic or hemorrhagic stroke were prospectively enrolled in the multicenter Stroke-Induced Pneumonia in Andalucía project between October 2014 and May 2016. Receiver operating characteristic curves and linear regression analyses were used to determine discrimination ability of the scores. The Hosmer-Lemeshow goodness-of-fit test and the plot of observed versus predicted SAP risk were used to assess model calibration. Among 201 included patients, SAP rate was 15.5% (31). Higher ISAN, A2DS2, and AIS-APS scores were related to SAP (all P manage SAP. The AIS-APS score would be recommendable for the development of future clinical trials. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Evaluating the benefits of incorporating traditional birth attendants in HIV prevention of mother to child transmission service delivery in Lilongwe, Malawi.

Science.gov (United States)

Hamela, Gloria; Kabondo, Charity; Tembo, Tapiwa; Zimba, Chifundo; Kamanga, Esmie; Mofolo, Innocent; Bulla, Bertha; Sellers, Christopher; Nakanga, R C; Lee, Clara; Martinson, Francis; Hoffman, Irving; van der Horst, Charles; Hosseinipour, Mina C

2014-03-01

The objective of our intervention was to examine the benefits of incorporating traditional birth attendants (TBA) in HIV Prevention of Mother to Child Transmission (PMTCT) service delivery. We developed a training curriculum for TBAs related to PMTCT and current TBA roles in Malawi. Fourteen TBAs and seven TBA assistants serving 4 urban health centre catchment areas were assessed, trained and supervised. Focus group discussions with the TBAs were conducted after implementation of the program. From March 2008 to August 2009, a total of 4017 pregnant women visited TBAs, out of which 2133 (53.1%) were directly referred to health facilities and 1,884 (46.9%) women delivered at TBAs and subsequently referred. 168 HIV positive women were identified by TBAs. Of these, 86/168 (51.2%) women received nevirapine and 46/168 (27.4%) HIV exposed infants received nevirapine. The challenges in providing PMTCT services included lack of transportation for referrals and absence of a reporting system to confirm the woman's arrival at the health center. Non-disclosure of HIV status by patients to the TBAs resulted in inability to assist nevirapine uptake. TBAs, when trained and well-supervised, can supplement efforts to provide PMTCT services in communities.

Decision-Tree Analysis for Predicting First-Time Pass/Fail Rates for the NCLEX-RN® in Associate Degree Nursing Students.

Science.gov (United States)

Chen, Hsiu-Chin; Bennett, Sean

2016-08-01

Little evidence shows the use of decision-tree algorithms in identifying predictors and analyzing their associations with pass rates for the NCLEX-RN(®) in associate degree nursing students. This longitudinal and retrospective cohort study investigated whether a decision-tree algorithm could be used to develop an accurate prediction model for the students' passing or failing the NCLEX-RN. This study used archived data from 453 associate degree nursing students in a selected program. The chi-squared automatic interaction detection analysis of the decision trees module was used to examine the effect of the collected predictors on passing/failing the NCLEX-RN. The actual percentage scores of Assessment Technologies Institute®'s RN Comprehensive Predictor(®) accurately identified students at risk of failing. The classification model correctly classified 92.7% of the students for passing. This study applied the decision-tree model to analyze a sequence database for developing a prediction model for early remediation in preparation for the NCLEXRN. [J Nurs Educ. 2016;55(8):454-457.]. Copyright 2016, SLACK Incorporated.

Efficacy of Scutellaria baicalensis for the Treatment of Hand, Foot, and Mouth Disease Associated with Encephalitis in Patients Infected with EV71: A Multicenter, Retrospective Analysis

Directory of Open Access Journals (Sweden)

Hailong Lin

2016-01-01

Full Text Available This study aimed to evaluate the clinical efficacy and safety of using the traditional Chinese herbal medicine Scutellaria baicalensis for the treatment of severe HFMD in 725 patients aged >1 year in a multicenter, retrospective analysis. The patients were divided into the S. baicalensis and ribavirin groups, and the temperatures, presence or absence of skin rashes and oral lesions, nervous system (NS involvement, and viral loads of the patients, as well as the safety of the treatments, were evaluated. The median duration of fever, median time to NS involvement, and the number of patients with oral ulcers and/or vesicles, as well as skin rashes, were decreased in the S. baicalensis group compared with the ribavirin group. In addition, the EV71 viral loads were decreased in the S. baicalensis group, suggesting that S. baicalensis exerted more potent antiviral effects compared with ribavirin. The present study demonstrated that S. baicalensis was suitable for the treatment of severe HFMD in patients aged >1 year, since it was shown to rapidly relieve fever, attenuate oral lesions and rashes, and improve NS involvement. Furthermore, it was demonstrated to be relatively safe for topical application.

Methimazole associated eosinophilic pleural effusion: a case report.

Science.gov (United States)

Gaspar-da-Costa, Pedro; Duarte Silva, Filipa; Henriques, Júlia; do Vale, Sónia; Braz, Sandra; Meneses Santos, João; M M Victorino, Rui

2017-03-21

Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.

Genomic prediction in contrast to a genome-wide association study in explaining heritable variation of complex growth traits in breeding populations of Eucalyptus.

Science.gov (United States)

Müller, Bárbara S F; Neves, Leandro G; de Almeida Filho, Janeo E; Resende, Márcio F R; Muñoz, Patricio R; Dos Santos, Paulo E T; Filho, Estefano Paludzyszyn; Kirst, Matias; Grattapaglia, Dario

2017-07-11

The advent of high-throughput genotyping technologies coupled to genomic prediction methods established a new paradigm to integrate genomics and breeding. We carried out whole-genome prediction and contrasted it to a genome-wide association study (GWAS) for growth traits in breeding populations of Eucalyptus benthamii (n =505) and Eucalyptus pellita (n =732). Both species are of increasing commercial interest for the development of germplasm adapted to environmental stresses. Predictive ability reached 0.16 in E. benthamii and 0.44 in E. pellita for diameter growth. Predictive abilities using either Genomic BLUP or different Bayesian methods were similar, suggesting that growth adequately fits the infinitesimal model. Genomic prediction models using ~5000-10,000 SNPs provided predictive abilities equivalent to using all 13,787 and 19,506 SNPs genotyped in the E. benthamii and E. pellita populations, respectively. No difference was detected in predictive ability when different sets of SNPs were utilized, based on position (equidistantly genome-wide, inside genes, linkage disequilibrium pruned or on single chromosomes), as long as the total number of SNPs used was above ~5000. Predictive abilities obtained by removing relatedness between training and validation sets fell near zero for E. benthamii and were halved for E. pellita. These results corroborate the current view that relatedness is the main driver of genomic prediction, although some short-range historical linkage disequilibrium (LD) was likely captured for E. pellita. A GWAS identified only one significant association for volume growth in E. pellita, illustrating the fact that while genome-wide regression is able to account for large proportions of the heritability, very little or none of it is captured into significant associations using GWAS in breeding populations of the size evaluated in this study. This study provides further experimental data supporting positive prospects of using genome-wide data to

Health effects associated with energy conservation measures in commercial buildings

International Nuclear Information System (INIS)

Stenner, R.D.; Baechler, M.C.

1990-09-01

Indoor air quality can conceivably be impacted by hundreds of different chemicals. More than 900 different organic compounds alone have been identified in indoor air. The health effects that could potentially arise from exposure to individual pollutants or mixtures of pollutants cover the full range of acute and chronic effects, including largely reversible responses, such as rashes and irritations, as well as irreversible toxic and carcinogenic effects. These indoor contaminants are emitted from a large variety of materials and substances that are widespread components of everyday life. Pacific Northwest Laboratory conducted a search of the peer-reviewed literature on health effects associated with indoor air contaminants for the Bonneville Power Administration to aid the agency in the preparation of environmental documents. The results of this search are reported in two volumes. Volume 1 is a summary of the results of the literature search; Volume 2 is the complete results of the literature search and contains all references to the material reviewed. 16 tabs

Health effects associated with energy conservation measures in commercial buildings

Energy Technology Data Exchange (ETDEWEB)

Stenner, R.D.; Baechler, M.C.

1990-09-01

Indoor air quality can conceivably be impacted by hundreds of different chemicals. More than 900 different organic compounds alone have been identified in indoor air. The health effects that could potentially arise from exposure to individual pollutants or mixtures of pollutants cover the full range of acute and chronic effects, including largely reversible responses, such as rashes and irritations, as well as irreversible toxic and carcinogenic effects. These indoor contaminants are emitted from a large variety of materials and substances that are widespread components of everyday life. Pacific Northwest Laboratory conducted a search of the peer-reviewed literature on health effects associated with indoor air contaminants for the Bonneville Power Administration to aid the agency in the preparation of environmental documents. The results of this search are reported in two volumes. Volume 1 is a summary of the results of the literature search; Volume 2 is the complete results of the literature search and contains all references to the material reviewed. 16 tabs.

Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers

Directory of Open Access Journals (Sweden)

Litonjua Augusto A

2011-06-01

Full Text Available Abstract Background Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs, while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics. Methods In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS SNPs ranked by Random Forests (RF importance score for the CAMP (Childhood Asthma Management Program population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group. Results Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors. Conclusions Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.

Asian Summer Monsoon Rainfall associated with ENSO and its Predictability

Science.gov (United States)

Shin, C. S.; Huang, B.; Zhu, J.; Marx, L.; Kinter, J. L.; Shukla, J.

2015-12-01

The leading modes of the Asian summer monsoon (ASM) rainfall variability and their seasonal predictability are investigated using the CFSv2 hindcasts initialized from multiple ocean analyses over the period of 1979-2008 and observation-based analyses. It is shown that the two leading empirical orthogonal function (EOF) modes of the observed ASM rainfall anomalies, which together account for about 34% of total variance, largely correspond to the ASM responses to the ENSO influences during the summers of the developing and decaying years of a Pacific anomalous event, respectively. These two ASM modes are then designated as the contemporary and delayed ENSO responses, respectively. It is demonstrated that the CFSv2 is capable of predicting these two dominant ASM modes up to the lead of 5 months. More importantly, the predictability of the ASM rainfall are much higher with respect to the delayed ENSO mode than the contemporary one, with the predicted principal component time series of the former maintaining high correlation skill and small ensemble spread with all lead months whereas the latter shows significant degradation in both measures with lead-time. A composite analysis for the ASM rainfall anomalies of all warm ENSO events in this period substantiates the finding that the ASM is more predictable following an ENSO event. The enhanced predictability mainly comes from the evolution of the warm SST anomalies over the Indian Ocean in the spring of the ENSO maturing phases and the persistence of the anomalous high sea surface pressure over the western Pacific in the subsequent summer, which the hindcasts are able to capture reasonably well. The results also show that the ensemble initialization with multiple ocean analyses improves the CFSv2's prediction skill of both ENSO and ASM rainfall. In fact, the skills of the ensemble mean hindcasts initialized from the four different ocean analyses are always equivalent to the best ones initialized from any individual ocean

Hepatitis C Eradication and Improvement of Cryoglobulinemia-Associated Rash and Membranoproliferative Glomerulonephritis with Interferon and Ribavirin after Kidney Transplantation

Directory of Open Access Journals (Sweden)

Marilyn Zeman

2006-01-01

Full Text Available Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant.

Associations between work environment and psychological distress after a workplace terror attack: the importance of role expectations, predictability and leader support.

Science.gov (United States)

Birkeland, Marianne Skogbrott; Nielsen, Morten Birkeland; Knardahl, Stein; Heir, Trond

2015-01-01

Experiencing terrorism is associated with high levels of psychological distress among survivors. The aim of the present study was to examine whether work environmental factors such as role clarity and predictability, role conflicts, and leader support may protect against elevated levels of psychological distress after a workplace terrorist attack. Data from approximately 1800 ministerial employees were collected ten months after the 2011 Oslo bombing attack which targeted the Norwegian ministries. The results show that after a traumatic event, lower role conflicts, higher role clarity, higher predictability, and higher leader support were independently associated with lower psychological distress. These findings suggest that the workplace environment may be a facilitator of employees' mental health after stressful events.

Climatic associations of British species distributions show good transferability in time but low predictive accuracy for range change.

Directory of Open Access Journals (Sweden)

Giovanni Rapacciuolo

Full Text Available Conservation planners often wish to predict how species distributions will change in response to environmental changes. Species distribution models (SDMs are the primary tool for making such predictions. Many methods are widely used; however, they all make simplifying assumptions, and predictions can therefore be subject to high uncertainty. With global change well underway, field records of observed range shifts are increasingly being used for testing SDM transferability. We used an unprecedented distribution dataset documenting recent range changes of British vascular plants, birds, and butterflies to test whether correlative SDMs based on climate change provide useful approximations of potential distribution shifts. We modelled past species distributions from climate using nine single techniques and a consensus approach, and projected the geographical extent of these models to a more recent time period based on climate change; we then compared model predictions with recent observed distributions in order to estimate the temporal transferability and prediction accuracy of our models. We also evaluated the relative effect of methodological and taxonomic variation on the performance of SDMs. Models showed good transferability in time when assessed using widespread metrics of accuracy. However, models had low accuracy to predict where occupancy status changed between time periods, especially for declining species. Model performance varied greatly among species within major taxa, but there was also considerable variation among modelling frameworks. Past climatic associations of British species distributions retain a high explanatory power when transferred to recent time--due to their accuracy to predict large areas retained by species--but fail to capture relevant predictors of change. We strongly emphasize the need for caution when using SDMs to predict shifts in species distributions: high explanatory power on temporally-independent records

Probability-based collaborative filtering model for predicting gene-disease associations.

Science.gov (United States)

Zeng, Xiangxiang; Ding, Ningxiang; Rodríguez-Patón, Alfonso; Zou, Quan

2017-12-28

Accurately predicting pathogenic human genes has been challenging in recent research. Considering extensive gene-disease data verified by biological experiments, we can apply computational methods to perform accurate predictions with reduced time and expenses. We propose a probability-based collaborative filtering model (PCFM) to predict pathogenic human genes. Several kinds of data sets, containing data of humans and data of other nonhuman species, are integrated in our model. Firstly, on the basis of a typical latent factorization model, we propose model I with an average heterogeneous regularization. Secondly, we develop modified model II with personal heterogeneous regularization to enhance the accuracy of aforementioned models. In this model, vector space similarity or Pearson correlation coefficient metrics and data on related species are also used. We compared the results of PCFM with the results of four state-of-arts approaches. The results show that PCFM performs better than other advanced approaches. PCFM model can be leveraged for predictions of disease genes, especially for new human genes or diseases with no known relationships.

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

Directory of Open Access Journals (Sweden)

Mugwaneza Placidie

2010-12-01

Full Text Available Abstract Background Mother-to-child transmission (MTCT of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV regimens for the prevention of MTCT (PMTCT; but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp to md-ARV regimens in a resource-limited setting. Methods Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy of sites providing PMTCT as a stand-alone service (stand-alone site versus sites providing PMTCT as well as antiretroviral therapy (ART (full package site. CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp prophylaxis and highly active antiretroviral therapy (HAART were analysed. Results From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+ during antenatal care (ANC. CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR = 1.3; 95% confidence interval (CI: 1.1-1.4. Enrolment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3. However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0. Conclusions All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT

High rates of regimen change due to drug toxicity among a cohort of South Indian adults with HIV infection initiated on generic, first-line antiretroviral treatment.

Science.gov (United States)

Sivadasan, Ajith; Abraham, O C; Rupali, Priscilla; Pulimood, Susanne A; Rajan, Joyce; Rajkumar, S; Zachariah, Anand; Kannangai, Rajesh; Kandathil, Abraham Joseph; Sridharan, G; Mathai, Dilip

2009-05-01

To determine the rates, reasons and predictors of treatment change of the initial antiretroviral treatment (ART) regimen in HIV-infected south Indian adults. In this prospective cohort study, ART-naive adults initiated on generic, fixed dose combination ART as per the National AIDS Control Organization guidelines were followed up at an academic medical center. Treatment change was defined as any event which necessitated a change in or discontinuation of the initial ART regimen. Two hundred and thirty persons with HIV infection (males 74.8% and median age 37 years) were followed up for median duration of 48 weeks. The majority (98.7%) had acquired HIV infection through the heterosexual route. Most (70.4%) had advanced IV infection (WHO clinical stage 3 or 4) and 78% had CD4+ T-lymphocyte counts below 200 cells/microL. The initial ART regimens used were: Lamivudine (3TC) with Stavudine (d4T) (in 76%) or Azidothymidine (AZT) and Nevirapine (NVP) (in 86%) or Efavirenz (EFV). The cumulative incidence of treatment change was 39.6% (91 patients). Drug toxicity (WHO grade 3 or 4) was the reason for treatment change among 62 (27%) (incidence rate 35.9/100 person-years). The most common toxicities were attributable to the thymidine analogue nucleoside reverse transcriptase inhibitors (NRTIs), d4T and AZT [lactic acidosis (8.7%), anemia (7%) and peripheral neuropathy (5.2%)]. The other toxicities were rash (3.9%) and hepatitis (1.3%) due to NVP. The mortality (4.6/100 person-years) and disease progression rates (4.1/100 person-years) were low. The ART regimens used in this study were effective in decreasing disease progression and death. However, they were associated with high rates of drug toxicities, particularly those attributable to thymidine analogue NRTI. As efforts are made to improve access to ART, treatment regimens chosen should not only be potent, but also safe.

Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies.

Science.gov (United States)

Hamers, Raph L; Sigaloff, Kim C E; Wensing, Annemarie M; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; Rinke de Wit, Tobias F; Schuurman, Rob

2012-06-01

Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case–control study

Science.gov (United States)

Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

2014-01-01

Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/A<0.92(n=59) to determine serum vascular biomarkers that were predictive of this vasculopathy. Outcome measures The primary outcome of this study was to identify a PA/A ratio in a cohort of individuals exposed to WTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of

Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.

Science.gov (United States)

Styczynski, Ashley R; Malta, Juliane M A S; Krow-Lucal, Elisabeth R; Percio, Jadher; Nóbrega, Martha E; Vargas, Alexander; Lanzieri, Tatiana M; Leite, Priscila L; Staples, J Erin; Fischer, Marc X; Powers, Ann M; Chang, Gwong-Jen J; Burns, P L; Borland, Erin M; Ledermann, Jeremy P; Mossel, Eric C; Schonberger, Lawrence B; Belay, Ermias B; Salinas, Jorge L; Badaro, Roberto D; Sejvar, James J; Coelho, Giovanini E

2017-08-01

In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

Predicting ideological prejudice

NARCIS (Netherlands)

Brandt, M.J.

2018-01-01

A major shortcoming of current models of ideological prejudice is that although they can anticipate the direction of the association between participants’ ideology and their prejudice against a range of target groups, they cannot predict the size of this association. I developed and tested models

Applied predictive control

CERN Document Server

Sunan, Huang; Heng, Lee Tong

2002-01-01

The presence of considerable time delays in the dynamics of many industrial processes, leading to difficult problems in the associated closed-loop control systems, is a well-recognized phenomenon. The performance achievable in conventional feedback control systems can be significantly degraded if an industrial process has a relatively large time delay compared with the dominant time constant. Under these circumstances, advanced predictive control is necessary to improve the performance of the control system significantly. The book is a focused treatment of the subject matter, including the fundamentals and some state-of-the-art developments in the field of predictive control. Three main schemes for advanced predictive control are addressed in this book: • Smith Predictive Control; • Generalised Predictive Control; • a form of predictive control based on Finite Spectrum Assignment. A substantial part of the book addresses application issues in predictive control, providing several interesting case studie...

Survival of HIV/AIDS patients with antiretroviral therapy in association with first-line regimens from 2007 – 2010 in Haji AdamMalik general hospital Medan

Science.gov (United States)

Kembaren, T.; Ginting, Y.; Saragih, R. H.

2018-03-01

The mortality related to AIDS have decreased dramatically among HIV infected patients taking HAART. HAART is the combination of at least 3 antiretroviral drugs based on the recommendation of WHO. The recent guideline for 1st line therapy recommended by the Indonesian Ministry of Health was Zidovudine/Lamivudine/Nevirapine (ZDV+3TC+NVP), Zidovudine/Lamivudine/Efavirenz (ZDV+3TC+EFV), Stavudine/Lamivudine/Nevirapine (d4T+3TC+NVP), Stavudine/Lamivudine/Efavirenz (d4T+3TC+EFV). Due to a side effect of Stavudine, Ministry of Health plan to pass out Stavudin from the regimens for 1stline therapy.We wanted to evaluate the survival of HIV/AIDS patients with first-line regimens in HAM general hospital Medan. A cohort retrospective study was conducted to evaluate the survival of HIV/AIDS patients taking a combination of 1st line antiretroviral therapy between January 2007 and December 2010. From 2007-2010, among 609 HIV/AIDS patients with first-line ARV medication, 77.5% were male, and 22.5% were female. The most common risk infection was heterosexual. The majority of the patients were in 25-34 years old group. Most of the patients with CD4 1-50 cell/mm3. 2 years survival rate in HIV/AIDS patients taking ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP, d4T+3TC+EFV were 61.5%, 61.2%, 57.5% and 59.3% respectively. There were no significant differences of 24 months survival in both regiment with or without d4T, 61.8% vs 63.6%.

Child Allergic Symptoms and Well-Being at School: Findings from ALSPAC, a UK Cohort Study.

Science.gov (United States)

Teyhan, Alison; Galobardes, Bruna; Henderson, John

2015-01-01

Eczema and asthma are common conditions in childhood that can influence children's mental health. Despite this, little is known about how these conditions affect the well-being of children in school. This study examines whether symptoms of eczema or asthma are associated with poorer social and mental well-being in school as reported by children and their teachers at age 8 years. Participants were from the Avon Longitudinal Study of Parents and Children. Measures of child well-being in school were child-reported (n = 6626) and teacher reported (n = 4366): children reported on their enjoyment of school and relationships with peers via a self-complete questionnaire; teachers reported child mental well-being using the Strengths and Difficulties Questionnaire [binary outcomes were high 'internalizing' (anxious/depressive) and 'externalizing' (oppositional/hyperactive) problems (high was >90th percentile)]. Child rash and wheeze status were maternally reported and symptoms categorised as: 'none'; 'early onset transient' (infancy/preschool only); 'persistent' (infancy/preschool and at school age); and 'late onset' (school age only). Children with persistent (OR 1.29, 95% CI 1.02 to 1.63) and late onset (OR 1.48, 95% CI 1.02 to 2.14) rash were more likely to report being bullied, and children with persistent wheeze to feel left out (OR 1.42, 95% CI 1.10 to 1.84). Late onset rash was associated with high teacher-reported internalising behaviours (OR 1.61, 95% CI 1.02 to 2.54), and persistent rash with high externalising behaviours (OR 1.37, 95% CI 1.02 to 1.84). Child sleep and maternal mental health explained some of the associations with teacher-reported mental well-being. Symptoms of eczema or asthma can adversely affect a child's social and mental well-being at primary school. This suggests interventions, such as additional support or education of peers, should begin at early stages in schooling.

Interactions between Internalizing Symptoms and Urgency in the Prediction of Alcohol Use and Expectancies among Low-Income, Minority Early Adolescents

Directory of Open Access Journals (Sweden)

Naomi R. Marmorstein

2015-01-01

Full Text Available This study examined whether urgency, a disposition to rash action under conditions of strong emotion, moderates associations between internalizing symptoms and alcohol use and related expectancies. Data from the Camden Youth Development Study, a longitudinal, community-based study of early adolescents ( N = 144, mean age at intake = 11.9 years; 65% Hispanic, 30% African-American; 50% male, were used. Self-report questionnaire measures of depressive symptoms, social and generalized anxiety symptoms, urgency, alcohol use, and alcohol expectancies were used. Mixed models were used to examine the effects of internalizing symptoms, urgency, and their interaction on alcohol use and expectancy trajectories over time. Depressive symptoms interacted with urgency such that youth with high levels of both tended to have elevated levels of global positive alcohol expectancies. Social anxiety symptoms interacted with urgency to be associated with increasing levels of social behavior alcohol expectancies such that youth with high levels of both tended to experience particular increases in these expectancies over time. Generalized anxiety was not found to be associated with alcohol-related constructs. Therefore, high levels of urgency combine with depressive and social anxiety symptoms to be associated with particularly increased risk for alcohol expectancies that are associated with later alcohol use and problems, indicating particular risk for youth with these combinations of personality traits and psychopathology symptoms.

Tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR) have distinct cutaneous toxicity profiles: a meta-analysis and review of the literature.

Science.gov (United States)

Massey, Paul R; Okman, Jonathan S; Wilkerson, Julia; Cowen, Edward W

2015-06-01

Inhibition of the vascular endothelial growth factor receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical trials. PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving ≥50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms. Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45-2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43-3.00), and pruritus (OR, 1.25; 95 % CI, 1.12-1.39) were associated with anti-VEGFR TKIs. Vandetanib had the highest incidence of rash (41 %), while sorafenib was most commonly associated with HFSR (37 %) and pruritus (14 %). The incidence of HFSR from 2000 to 2013 showed an upward trend (r (2) = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r (2) = 0.237, p = 0.04). The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.

Uncertainties associated with lacking data for predictions of solid-solution partitioning of metals in soil

International Nuclear Information System (INIS)

Le, T.T. Yen; Hendriks, A. Jan

2014-01-01

Soil properties, i.e., pH and contents of soil organic matter (SOM), dissolved organic carbon (DOC), clay, oxides, and reactive metals, are required inputs to both mechanistic and empirical modeling in assessing metal solid-solution partitioning. Several of these properties are rarely measured in site-specific risk assessment. We compared the uncertainties induced by lacking data on these soil properties in estimating metal soil solution concentrations. The predictions by the Orchestra framework were more sensitive to lacking soil property data than the predictions by the transfer functions. The deviations between soil solution concentrations of Cd, Ni, Zn, Ba, and Co estimated with measured SOM and those estimated with generic SOM by the Orchestra framework were about 10 times larger than the deviations in the predictions by the transfer functions. High uncertainties were induced by lacking data in assessing solid-solution partitioning of oxy-anions like As, Mo, Sb, Se, and V. Deviations associated with lacking data in predicting soil solution concentrations of these metals by the Orchestra framework reached three-to-six orders of magnitude. The solid-solution partitioning of metal cations was strongly influenced by pH and contents of organic matter, oxides, and reactive metals. Deviations of more than two orders of magnitude were frequently observed between the estimates of soil solution concentrations with the generic values of these properties and the estimates based on the measured data. Reliable information on these properties is preferred to be included in the assessment by either the Orchestra framework or transfer functions. - Highlights: • Estimates of metal solid-solution partitioning sensitive to soil property data. • Uncertainty mainly due to lacking reactive metal contents, pH, and organic matter. • Soil solution concentrations of oxy-anions highly influenced by oxide contents. • Clay contents had least effects on solid-solution partitioning

Uncertainties associated with lacking data for predictions of solid-solution partitioning of metals in soil

Energy Technology Data Exchange (ETDEWEB)

Le, T.T. Yen, E-mail: YenLe@science.ru.nl; Hendriks, A. Jan

2014-08-15

Soil properties, i.e., pH and contents of soil organic matter (SOM), dissolved organic carbon (DOC), clay, oxides, and reactive metals, are required inputs to both mechanistic and empirical modeling in assessing metal solid-solution partitioning. Several of these properties are rarely measured in site-specific risk assessment. We compared the uncertainties induced by lacking data on these soil properties in estimating metal soil solution concentrations. The predictions by the Orchestra framework were more sensitive to lacking soil property data than the predictions by the transfer functions. The deviations between soil solution concentrations of Cd, Ni, Zn, Ba, and Co estimated with measured SOM and those estimated with generic SOM by the Orchestra framework were about 10 times larger than the deviations in the predictions by the transfer functions. High uncertainties were induced by lacking data in assessing solid-solution partitioning of oxy-anions like As, Mo, Sb, Se, and V. Deviations associated with lacking data in predicting soil solution concentrations of these metals by the Orchestra framework reached three-to-six orders of magnitude. The solid-solution partitioning of metal cations was strongly influenced by pH and contents of organic matter, oxides, and reactive metals. Deviations of more than two orders of magnitude were frequently observed between the estimates of soil solution concentrations with the generic values of these properties and the estimates based on the measured data. Reliable information on these properties is preferred to be included in the assessment by either the Orchestra framework or transfer functions. - Highlights: • Estimates of metal solid-solution partitioning sensitive to soil property data. • Uncertainty mainly due to lacking reactive metal contents, pH, and organic matter. • Soil solution concentrations of oxy-anions highly influenced by oxide contents. • Clay contents had least effects on solid-solution partitioning

Skin diseases associated with Agent Orange and other organochlorine exposures.

Science.gov (United States)

Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

2016-01-01

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

Contaminants of emerging concern in the Hartbeespoort Dam catchment and the uMngeni River estuary 2016 pollution incident, South Africa.

Science.gov (United States)

Rimayi, Cornelius; Odusanya, David; Weiss, Jana M; de Boer, Jacob; Chimuka, Luke

2018-06-15

A quantitative assessment of pollutants of emerging concern in the Hartbeespoort Dam catchment area was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to establish the occurrence, source and distribution of 15 environmental pollutants, including 10 pharmaceuticals, 1 pesticide and 4 steroid hormones. Seasonal sampling was conducted in the Hartbeespoort Lake using sub-surface grab sampling to determine the lake's ecological status and obtain data for establishment of progressive operational monitoring. The Jukskei River, which lies upstream of the Hartbeespoort Dam, was sampled in the winter season. Five year old carp (Cyprinus carpio) and catfish (Clarias gariepinus) were also sampled from the Hartbeespoort Dam to study bioaccumulation in biota as well as to estimate risk associated with fish consumption. In the Jukskei River, the main source of 11 emerging pollutants (EPs) was identified as raw sewage overflow, with the highest ∑11 EP concentration of 593ngL -1 being recorded at the Midrand point and the lowest ∑11 EP concentration of 164ngL -1 at the N14 site located 1km downstream of a large wastewater treatment plant. The Jukskei River was found to be the largest contributor of the emerging contaminants detected in the Hartbeespoort Dam. In the Hartbeespoort Dam EP concentrations were generally in the order efavirenz>nevirapine>carbamazepine>methocarbamol>bromacil>venlafaxine. Water and sediment were sampled from the uMngeni River estuary within 24h after large volumes of an assortment of pharmaceutical waste had been discovered to be washed into the river estuary after flash rainfall on 18 May 2016. Analytical results revealed high levels of some emerging pollutants in sediment samples, up to 81ngg -1 for nevirapine and 4ngg -1 for etilefrine HCL. This study shows that efavirenz, nevirapine, carbamazepine, methocarbamol, bromacil and venlafaxine are contaminants that require operational monitoring in South African urban waters

Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

Science.gov (United States)

Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

2018-05-03

We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

78 FR 20925 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Science.gov (United States)

2013-04-08

... hydrochloride Desvenlafaxine Dutasteride; tamsulosin hydrochloride E Estramustine phosphate sodium Ethinyl... tromethamine L Loratadine M Miconazole Minocycline hydrochloride Mitotane N Nevirapine P Phentermine hydrochloride; topiramate R Rimexolone Rizatriptan benzoate [[Page 20926

Trial-by-Trial Modulation of Associative Memory Formation by Reward Prediction Error and Reward Anticipation as Revealed by a Biologically Plausible Computational Model.

Science.gov (United States)

Aberg, Kristoffer C; Müller, Julia; Schwartz, Sophie

2017-01-01

Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images. Individual sensitivities to reward and punishment have been found to influence the activation of the dopaminergic reward system and could therefore help explain these seemingly discrepant results. Here, we used a novel associative memory task combined with computational modeling and showed independent effects of reward-delivery and reward-anticipation on memory. Strikingly, the computational approach revealed positive influences from both reward delivery, as mediated by prediction error magnitude, and reward anticipation, as mediated by magnitude of expected value, even in the absence of behavioral effects when analyzed using standard methods, i.e., by collapsing memory performance across trials within conditions. We additionally measured trait estimates of reward and punishment sensitivity and found that individuals with increased reward (vs. punishment) sensitivity had better memory for associations encoded during positive (vs. negative) prediction errors when tested after 20 min, but a negative trend when tested after 24 h. In conclusion, modeling trial-by-trial fluctuations in the magnitude of reward, as we did here for prediction errors and expected value computations, provides a comprehensive and biologically plausible description of

Genome-Wide Association Studies and Comparison of Models and Cross-Validation Strategies for Genomic Prediction of Quality Traits in Advanced Winter Wheat Breeding Lines

Directory of Open Access Journals (Sweden)

Peter S. Kristensen

2018-02-01

Full Text Available The aim of the this study was to identify SNP markers associated with five important wheat quality traits (grain protein content, Zeleny sedimentation, test weight, thousand-kernel weight, and falling number, and to investigate the predictive abilities of GBLUP and Bayesian Power Lasso models for genomic prediction of these traits. In total, 635 winter wheat lines from two breeding cycles in the Danish plant breeding company Nordic Seed A/S were phenotyped for the quality traits and genotyped for 10,802 SNPs. GWAS were performed using single marker regression and Bayesian Power Lasso models. SNPs with large effects on Zeleny sedimentation were found on chromosome 1B, 1D, and 5D. However, GWAS failed to identify single SNPs with significant effects on the other traits, indicating that these traits were controlled by many QTL with small effects. The predictive abilities of the models for genomic prediction were studied using different cross-validation strategies. Leave-One-Out cross-validations resulted in correlations between observed phenotypes corrected for fixed effects and genomic estimated breeding values of 0.50 for grain protein content, 0.66 for thousand-kernel weight, 0.70 for falling number, 0.71 for test weight, and 0.79 for Zeleny sedimentation. Alternative cross-validations showed that the genetic relationship between lines in training and validation sets had a bigger impact on predictive abilities than the number of lines included in the training set. Using Bayesian Power Lasso instead of GBLUP models, gave similar or slightly higher predictive abilities. Genomic prediction based on all SNPs was more effective than prediction based on few associated SNPs.

Food compounds inhibit Staphylococcus aureus bacteria and the toxicity of Staphylococcus Enterotoxin A (SEA) associated with atopic dermatitis

Science.gov (United States)

Atopic dermatitis or eczema is characterized by skin rashes and itching is an inflammatory disease that affects 10-20% of children and 1-3% of adults. Staphylococcus aureus bacteria are present on the skin of nearly all patients with atopic dermatitis. Antibiotics that suppress colonization of S. au...

[Severe Mast Cell Activation Syndrome in a 15-year-old patient with an hypermobile Ehlers-Danlos syndrome].

Science.gov (United States)

Daens, S; Grossin, D; Hermanns-Lê, T; Peeters, D; Manicourt, D

2018-02-01

We report the history of a 15-year old patient with a hypermobile Ehlers-Danlos syndrome (hEDS) (his mother, his two brothers and his sister have the same phenotype as him). He suffers mainly from a severe mast cell activation syndrome (MCAS) with an overreaction of the skin to any kind of contact (water of the shower, clothes, bed sheets) but he has also fatigue, headaches, and rash. This impressive rash is exacerbated after the shower and he has the urge to rest («shower's sign»). We describe the MCAS and its easy, fast and very effective medication management, without any significant side effects as well as its frequent association with the hEDS. We finally introduce the original term of «MASED» to this MCAS, associated, linked or entangled to hEDS.

Effective induction therapy for anti-SRP associated myositis in childhood: A small case series and review of the literature.

Science.gov (United States)

Binns, E L; Moraitis, E; Maillard, S; Tansley, S; McHugh, N; Jacques, T S; Wedderburn, L R; Pilkington, C; Yasin, S A; Nistala, K

2017-10-31

Anti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation. Three new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness. A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found. This paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients.

Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.

Science.gov (United States)

Sinxadi, Phumla Z; Dave, Joel A; Samuels, David C; Heckmann, Jeannine M; Maartens, Gary; Levitt, Naomi S; Wester, C William; Haas, David W; Hulgan, Todd

2013-07-01

Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used. Sequencing and Phylotree determined African mtDNA subhaplogroups. Wilcoxon and regression analyses determined associations between mtDNA subhaplogroups and ART-related complications. The 171 participants represented six major haplogroups: L0 (n=78), L1 (n=3), L2 (n=30), L3 (n=53), L4 (n=1), and L5 (n=6). Analyses were restricted to 161 participants representing L0, L2, and L3: 78% were female; the median age was 36 years. All had been exposed to thymidine analogues, 42% were on lopinavir/ritonavir (lopinavir/r), and 58% were on either efavirenz or nevirapine. Median (IQR) ART duration was 22 (14-36) months. Median fasting triglycerides were 1.60 (1.13-1.75) and 1.04 (0.83-1.45) mmol/liter among L3e1 (n=22) and other subhaplogroups, respectively (p=0.003). Subhaplogroup L3e1 [adjusted OR (aOR) 3.16 (95% CI: 1.11-8.96); p=0.03] and exposure to lopinavir/r [aOR 2.98 (95% CI: 1.02-8.96); p=0.05] were independently associated with hypertriglyceridemia, after adjusting for age, sex, and ART duration. There were no significant associations between mtDNA haplogroups and cholesterol, dysglycemia, hyperlactatemia, or lipoatrophy, or DSP. Subhaplogroup L3e1 and lopinavir/r exposure were independently associated with hypertriglyceridemia in black South Africans on ART. This is the first report to link an African mtDNA variant with hypertriglyceridemia. If replicated, these findings may provide new insights into host factors affecting metabolic complications.

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS).

Science.gov (United States)

Kuemmerle-Deschner, Jasmin B; Ozen, Seza; Tyrrell, Pascal N; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M

2017-06-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (pCAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Error associated with model predictions of wildland fire rate of spread

Science.gov (United States)

Miguel G. Cruz; Martin E. Alexander

2015-01-01

How well can we expect to predict the spread rate of wildfires and prescribed fires? The degree of accuracy in model predictions of wildland fire behaviour characteristics are dependent on the model's applicability to a given situation, the validity of the model's relationships, and the reliability of the model input data (Alexander and Cruz 2013b#. We...

SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

International Nuclear Information System (INIS)

Alsbeih, Ghazi; El-Sebaie, Medhat; Al-Harbi, Najla; Al-Hadyan, Khaled; Shoukri, Mohamed; Al-Rajhi, Nasser

2013-01-01

Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy

Low vitamin D does not predict statin associated muscle symptoms but is associated with transient increases in muscle damage and pain.

Science.gov (United States)

Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

2017-01-01

Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS. SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial. Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment was not different between patients who did (31.7 ± 12.1 ng/mL, n = 43) or did not (31.6 ± 10.3 ng/mL, n = 77) develop SAMS and did not predict SAMS (p = 0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2 ± 8.3 ng/mL, respectively) and did not predict SAMS (p = 0.96). The proportion of patients classified as VITD deficient (statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p = 0.01 and 0.02, respectively), independent of SAMS (p = 0.36 and 0.35). Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Case report: a novel KERA mutation associated with cornea plana and its predicted effect on protein function

DEFF Research Database (Denmark)

Roos, Laura; Bertelsen, Birgitte; Harris, Pernille

2015-01-01

individuals, hypotrichosis was found. KERA was screened for mutations using Sanger sequencing. We detected a novel KERA variant, p.(Ile225Thr), that segregates with the disease in the homozygous form. The three-dimensional structure of keratocan protein was modelled, and we showed that this missense variation...... of the keratocan gene (KERA) on chromosome 12q22. To date, only nine different disease-associated KERA mutations, including four missense mutations, have been described. Case presentation: In this report, we present clinical data from a Turkish family with autosomal recessive cornea plana. In some of the affected...... are predicted to result in destabilization of the protein. Conclusion: We present the 10th pathogenic KERA mutation identified so far. Protein modelling is a useful tool in predicting the effect of missense mutations. This case underline the importance of the leucin rich repeat domain for the protein function...

Post-traumatic stress symptom clusters in acute whiplash associated disorder and their prediction of chronic pain-related disability.

Science.gov (United States)

Maujean, Annick; Gullo, Matthew J; Andersen, Tonny Elmose; Ravn, Sophie Lykkegaard; Sterling, Michele

2017-11-01

The presence of post-traumatic stress disorder (PTSD) symptoms has been found to be associated with an increased risk of persisting neck pain and disability in motor vehicle crash (MVC) survivors with whiplash injuries. The findings are mixed as to which PTSD symptom(s) best predicts recovery in this population. The aims were (1) to explore the factor structure of the Post-traumatic Stress Diagnostic Scale (PDS) in a sample of acute whiplash-injured individuals following a MVC and (2) to identify the PTSD-symptom clusters that best predict long-term neck pain-related disability in this population as measured by the Neck Pain Disability Index (NDI). A sample (N = 146) of whiplash-injured individuals completed the NDI and the PDS at baseline (whiplash-injured individuals following a MVC.

Genome-Wide Locations of Potential Epimutations Associated with Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Using a Sequential Machine Learning Prediction Approach.

Science.gov (United States)

Haque, M Muksitul; Holder, Lawrence B; Skinner, Michael K

2015-01-01

Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation involves germline transmitted epimutations. The primary epimutations identified involve altered differential DNA methylation regions (DMRs). Different environmental toxicants have been shown to promote exposure (i.e., toxicant) specific signatures of germline epimutations. Analysis of genomic features associated with these epimutations identified low-density CpG regions (machine learning computational approach to predict all potential epimutations in the genome. A number of previously identified sperm epimutations were used as training sets. A novel machine learning approach using a sequential combination of Active Learning and Imbalance Class Learner analysis was developed. The transgenerational sperm epimutation analysis identified approximately 50K individual sites with a 1 kb mean size and 3,233 regions that had a minimum of three adjacent sites with a mean size of 3.5 kb. A select number of the most relevant genomic features were identified with the low density CpG deserts being a critical genomic feature of the features selected. A similar independent analysis with transgenerational somatic cell epimutation training sets identified a smaller number of 1,503 regions of genome-wide predicted sites and differences in genomic feature contributions. The predicted genome-wide germline (sperm) epimutations were found to be distinct from the predicted somatic cell epimutations. Validation of the genome-wide germline predicted sites used two recently identified transgenerational sperm epimutation signature sets from the pesticides dichlorodiphenyltrichloroethane (DDT) and methoxychlor (MXC) exposure lineage F3 generation. Analysis of this positive validation data set showed a 100% prediction accuracy for all the DDT-MXC sperm epimutations. Observations further elucidate the genomic features associated with transgenerational germline epimutations and identify a genome

Bull's-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of Identification of Erythema Migrans

Science.gov (United States)

Aucott, John N.; Crowder, Lauren A.; Yedlin, Victoria; Kortte, Kathleen B.

2012-01-01

Introduction. Lyme disease is an emerging worldwide infectious disease with major foci of endemicity in North America and regions of temperate Eurasia. The erythema migrans rash associated with early infection is found in approximately 80% of patients and can have a range of appearances including the classic target bull's-eye lesion and nontarget appearing lesions. Methods. A survey was designed to assess the ability of the general public to distinguish various appearances of erythema migrans from non-Lyme rashes. Participants were solicited from individuals who visited an educational website about Lyme disease. Results. Of 3,104 people who accessed a rash identification survey, 72.7% of participants correctly identified the classic target erythema migrans commonly associated with Lyme disease. A mean of 20.5% of participants was able to correctly identify the four nonclassic erythema migrans. 24.2% of participants incorrectly identified a tick bite reaction in the skin as erythema migrans. Conclusions. Participants were most familiar with the classic target erythema migrans of Lyme disease but were unlikely to correctly identify the nonclassic erythema migrans. These results identify an opportunity for educational intervention to improve early recognition of Lyme disease and to increase the patient's appropriate use of medical services for early Lyme disease diagnosis. PMID:23133445

Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

Science.gov (United States)

Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

2016-12-10

The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

Febrile urticaria in a family: uncommon manifestation of a common disease.