bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite
Authors: Saifullah Bullo , Hussein Mohd Zobir , Hussein-Al-Ali Samer Hasan , Arulselvan Palanisamy , Fakurazi Sharida 
Published: April 2013

Abstract

Background
Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6–24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.
Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.

Result
An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner.

Conclusions
Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis.
Identification of Trypanosoma cruzi Discrete Typing Units (DTUs) through the implementation of a High-Resolution Melting (HRM) genotyping assay
Authors: Higuera Sonia L , Guhl Felipe , Ramírez Juan David 
Published: April 2013

Abstract

Background
Chagas disease, caused by Trypanosoma cruzi, is a geographically widespread anthropozoonosis that is considered a major public health problem in Latin America. Because this parasite presents high genetic variability, a nomenclature has been adopted to classify the parasite into six discrete typing units (DTUs): TcI, TcII, TcIII, TcIV, TcV, and TcVI, which present different eco-epidemiological, clinical, and geographic associations. Currently, the available genotyping methods present a series of drawbacks that implies the need for developing new methods for characterizing T. cruzi DTU’s. The aim of this work was to genotype reference populations from T. cruzi by means of a High-Resolution Melting (HRM) genotyping assay.
To genotype the DTUs of 38 strains and 14 reference clones of T. cruzi from diverse sources, real-time PCR (qPCR) was coupled to high-resolution melting (HRM) based on the amplification of two molecular markers—the divergent domain of the 24 sα rRNA gene and the intergenic region of the mini-exon gene.

Findings
Amplification of the mini-exon gene allowed the genotyping of three distinct groups: TcI, TcII- TcIV- TcV, and TcIII-TcVI, while amplification of the 24sα gene generated non-overlapping melting temperature ranges for each DTU that were used to identify the groups in the six existing DTUs of Trypanosoma cruzi.

Conclusions
The proposed genotyping assay allowed discrimination of the six genetic groups by obtaining specific melting curves for each DTU. The application of this technique is proposed because of its specificity, sensitivity, high performance, and low cost compared with other previously described characterization methods.
Review of Economics and Cost-Effectiveness Analyses of Anticoagulant Therapy for Stroke Prevention in Atrial Fibrillation in the US
Authors: von Schéele Birgitta , Fernandez Maria , Hogue Susan Lynn , Kwong Winghan Jacqueline 
Published: April 2013

OBJECTIVE To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. DATA SOURCES A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. STUDY SELECTION AND DATA EXTRACTION The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. DATA SYNTHESIS Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from random ized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0–3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. CONCLUSIONS This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness research conducted in the real-world setting.
Characterization of Unbound Phenytoin Concentrations in Neurointensive Care Unit Patients Using a Revised Winter-Tozer Equation
Authors: Kane Sean P , Bress Adam P , Tesoro Eljim P 
Published: April 2013

BACKGROUND Prior studies examining the accuracy of the Winter-Tozer (WT) equation for correcting total phenytoin concentrations in critically ill patients have yielded conflicting results and are limited by small sample sizes and stringent exclusion criteria, which lessen external validity. OBJECTIVE To determine whether the traditional WT equation is appropriate in correcting total phenytoin concentrations in a large sample of patients in a neurointensive care unit (NICU) and whether a new equation may be more predictive. METHODS In a retrospective study, NICU patients with reports of a concurrent total and unbound phenytoin concentration and albumin level were analyzed. Two new predictive equations were generated using a revised WT equation and regression model of baseline and laboratory characteristics. Prediction error analysis using a 20% validation cohort was conducted on all 3 equations for comparison. RESULTS A total of 140 adults were included for data analysis, with data on 80% used for derivation and 20% as validation of all equations. The mean unbound phenytoin concentration was 1.4 μg/mL, which represented a free fraction of 10%. Most samples were collected within 24 hours of NICU admission. Multivariate regression analysis demonstrated that albumin, total phenytoin concentration, sex, and creatinine clearance were predictive of measured unbound phenytoin concentrations. The traditional WT equation significantly underpredicted true unbound phenytoin concentrations, with 32.1% of patients having a prediction error of more than 50% in the validation cohort. CONCLUSIONS The traditional WT equation was significantly biased in underpredicting true unbound phenytoin concentrations in neurointensive care unit patients and should not be used in this setting. Two modified equations were more accurate and precise and should be considered for use when unbound phenytoin concentrations are not readily available in an NICU population.
Effect of the Human Chorionic Gonadotropin Diet on Patient Outcomes
Authors: Goodbar Nancy H , Foushee Jaime A , Eagerton David H , Haynes Katie B , Johnson Amanda A 
Published: April 2013

OBJECTIVE To report a case of left lower extremity deep vein thrombosis (DVT) and bilateral pulmonary embolisms in a patient who initiated the human chorionic gonadotropin (HCG) diet 2 weeks prior to presentation. CASE SUMMARY A 64-year-old white female presented with leg swelling and shortness of breath. Lower extremity ultrasound revealed left leg DVT, and a computed tomography angiogram revealed bilateral pulmonary embolisms. A complete history and physical examination were unremarkable for any risk factors for acute thrombosis, with the exception of the initiation of the HCG diet approximately 2 weeks prior to presentation; the patient was taking 20 sublingual drops of HCG twice daily. Results of her hypercoagulable workup were negative. Upon admission, therapy was started with enoxaparin 120 mg subcutaneously twice daily and warfarin 5 mg orally once daily. According to the Naranjo probability scale, initiation of the HCG diet was a probable cause of our patient's adverse effects. DISCUSSION The HCG diet has very few efficacy studies and no significant safety studies associated with its use. Six relevant studies were identified for assessment of efficacy, and only 1 was associated with a significant weight reduction in the HCG diet study population. All of these studies evaluated the use of the HCG diet via injections of the hormone and significant calorie restriction, which is known as the Simeons method. Currently marketed HCG products include sublingual drops, lozenges, and pellets, but none of these methods has an evidence-based efficacy and safety standard. CONCLUSIONS As popularity of the HCG diet continues to increase, so do the potential adverse events associated with the management of weight loss via an unproven strategy. Patient safety information regarding this dieting strategy should be recognized by medical professionals.
Accidental Overdose of Intrathecal Cytarabine in Children
Authors: Thienprayoon Rachel , Heym Kenneth M , Pelfrey Lindsay , Bowers Daniel C 
Published: April 2013

OBJECTIVE To report 2 cases of intrathecal cytarabine overdose in children with cancer, neither of whom underwent cerebrospinal fluid (CSF) exchange per current recommendations or developed apparent toxicity related to the event. CASE SUMMARY A 17-year-old female with newly diagnosed acute myeloid leukemia received 177 mg of intrathecal cytarabine rather than the appropriate dose of 70 mg. She was monitored closely with no apparent toxicity from the event. A 4-year-old boy with newly diagnosed precursor B-cell acute lymphoblastic leukemia received 175 mg of intrathecal cytarabine rather than the appropriate dose of 70 mg. CSF was immediately withdrawn and intrathecal hydrocortisone was instilled for possible antiinflammatory effect. He developed no apparent toxicity from the event. DISCUSSION Cytarabine is an important chemotherapeutic agent in the treatment of leukemia. One case report of intrathecal cytarabine overdose was identified in the literature, which recommended CSF exchange as management. Neither child in our report underwent CSF exchange or developed apparent toxicity related to the event. Institutional changes were made in both cases to prevent similar events. CONCLUSIONS These cases demonstrate that measures such as CSF exchange are not uniformly required for cytarabine overdose.
High-Resolution Profiling of Fetal DNA Clearance from Maternal Plasma by Massively Parallel Sequencing
Authors: Yu Stephanie CY , Lee Shara WY , Jiang Peiyong , Leung Tak Y , Chan KC Allen , Chiu Rossa WK , Lo YM Dennis 
Published: April 2013

BACKGROUNDWith the advent of massively parallel sequencing (MPS), DNA analysis can now be performed in a genomewide manner. Recent studies have demonstrated the high precision of MPS for quantifying fetal DNA in maternal plasma. In addition, paired-end sequencing can be used to determine the size of each sequenced DNA fragment. We applied MPS in a high-resolution investigation of the clearance profile of circulating fetal DNA.METHODSUsing paired-end MPS, we analyzed serial samples of maternal plasma collected from 13 women after cesarean delivery. We also studied the transrenal excretion of circulating fetal DNA in 3 of these individuals by analyzing serial urine samples collected after delivery.RESULTSThe clearance of circulating fetal DNA occurred in 2 phases, with different kinetics. The initial rapid phase had a mean half-life of approximately 1 h, whereas the subsequent slow phase had a mean half-life of approximately 13 h. The final disappearance of circulating fetal DNA occurred at about 1 to 2 days postpartum. Although transrenal excretion was involved in the clearance of circulating fetal DNA, it was not the major route. Furthermore, we observed significant changes in the size profiles of circulating maternal DNA after delivery, but we did not observe such changes in circulating fetal DNA.CONCLUSIONSMPS of maternal plasma and urinary DNA permits high-resolution study of the clearance profile of circulating fetal DNA.
Genetic Information and the Prediction of Incident Type 2 Diabetes in a High-Risk Multiethnic Population
Authors: Anand Sonia S. , Meyre David , Pare Guillaume , Bailey Swneke D. , Xie Changchun , Zhang Xiaohe , Montpetit Alexandre , Desai Dipika , Bosch Jackie , Mohan Viswanathan , Diaz Rafael , McQueen Matthew J. , Cordell Heather J. , Keavney Bernard , Yusuf Salim , Gaudet Daniel , Gerstein Hertzel , Engert James C. ,   on behalf of the EpiDREAM Genetics Investigators
Published: April 2013

OBJECTIVE
To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.

RESEARCH DESIGN AND METHODS
In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.

RESULTS
Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05–1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691–0.725) and increased only marginally to 0.714 (0.698–0.731) with the addition of the gene score (P for C statistic change = 0.0052).

CONCLUSIONS
T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.
Secular Changes in U.S. Prediabetes Prevalence Defined by Hemoglobin A1c and Fasting Plasma Glucose
Authors: Bullard Kai McKeever , Saydah Sharon H. , Imperatore Giuseppina , Cowie Catherine C. , Gregg Edward W. , Geiss Linda S. , Cheng Yiling J. , Rolka Deborah B. , Williams Desmond E. , Caspersen Carl J. 
Published: April 2013

OBJECTIVE
Using a nationally representative sample of the civilian noninstitutionalized U.S. population, we estimated prediabetes prevalence and its changes during 1999–2010.

RESEARCH DESIGN AND METHODS
Data were from 19,182 nonpregnant individuals aged ≥12 years who participated in the 1999–2010 National Health and Nutrition Examination Surveys. We defined prediabetes as hemoglobin A1c (A1C) 5.7 to &lt;6.5% (39 to &lt;48 mmol/mol, A1C5.7) or fasting plasma glucose (FPG) 100 to &lt;126 mg/dL (impaired fasting glucose [IFG]). We estimated the prevalence of prediabetes, A1C5.7, and IFG for 1999–2002, 2003–2006, and 2007–2010. We calculated estimates age-standardized to the 2000 U.S. census population and used logistic regression to compute estimates adjusted for age, sex, race/ethnicity, poverty-to-income ratio, and BMI. Participants with self-reported diabetes, A1C ≥6.5% (≥48 mmol/mol), or FPG ≥126 mg/dL were included.

RESULTS
Among those aged ≥12 years, age-adjusted prediabetes prevalence increased from 27.4% (95% CI 25.1–29.7) in 1999–2002 to 34.1% (32.5–35.8) in 2007–2010. Among adults aged ≥18 years, the prevalence increased from 29.2% (26.8–31.8) to 36.2% (34.5–38.0). As single measures among individuals aged ≥12 years, A1C5.7 prevalence increased from 9.5% (8.4–10.8) to 17.8% (16.6–19.0), a relative increase of 87%, whereas IFG remained stable. These prevalence changes were similar among the total population, across subgroups, and after controlling for covariates.

CONCLUSIONS
During 1999–2010, U.S. prediabetes prevalence increased because of increases in A1C5.7. Continuous monitoring of prediabetes is needed to identify, quantify, and characterize the population of high-risk individuals targeted for ongoing diabetes primary prevention efforts.
Charos et l'Histoire dans les chansons populaires grecques
Authors: Saunier Guy 
Published: April 2013

Partant de la construction préalable d'une évolution de la conception populaire du mal contemporaine de l'oppression étrangère, l'étude recherche dans l'image du personnage de Charos des traces de réalités historiques durables.
Elle retient : a) le motif de la tente, objet militaire, lié au geste de la saisie par les cheveux, qui devient un signe d'iniquité ; b) la représentation permanente de Charos sous les traits d'un pillard, pirate ou envahisseur ; c) l'image du cortège des morts, ressenti à époque récente comme un cortège de prisonniers.
L'action de Charos est presque constamment définie comme une surenchère sur celle des oppresseurs mais on assiste pourtant à une imbrication progressive des deux univers : mort et oppression.
Investir et grandir : des rituels pour étayer le « je »
Authors: Hatchuel Françoise 
Published: April 2013

À partir d’une définition du « faire grandir » comme modalité de soutien de la capacité à investir, l’article montre, à l’articulation de l’anthropologie et de la psychanalyse, en quoi les rituels traditionnels de passage à l’âge adulte peuvent étayer la constitution du « Je » et comment, lorsque le monde extérieur peine à fournir des certitudes symboliques, des espaces d’élaboration deviennent nécessaires pour assurer cette fonction.
Contribution des rites à la suppléance familiale
Authors: Raveneau Gilles 
Published: April 2013

Partant d’une recherche ethnographique dans deux Maisons d’enfants à caractère social (MECS), cet article interroge la manière dont le rite et la ritualisation peuvent contribuer à la suppléance familiale. On examine les conditions favorables à l’apparition et à l’utilisation des rites et l’on observe comment ils peuvent être des outils possibles d’inclusion et de participation sociale, associés à la production d’une culture morale et éducative. On fait l’hypothèse que la psychologisation « sauvage » des problèmes par les professionnels et le recours quasi exclusif aux psychologues cliniciens comme régulateur des difficultés dans ces institutions tendent à sous-évaluer l’intérêt et l’efficacité des rituels, au profit de la seule « clinique de la parole ».
L'adolescence à l'épreuve de la neurobiologie ?
Authors: Georgieff Nicolas 
Published: April 2013

L’éclairage « cérébral » de l’adolescence permet de montrer que se joue à cette période un processus complexe d’interaction entre l’environnement et l’organisation cérébrale capable de remodeler celle-ci en fonction de nouvelles contraintes, tant extrinsèques qu’intrinsèques. Social, psychologique et biologique interagissent, le cerveau prenant en quelque sorte l’empreinte à la fois des changements du monde extérieur et des contraintes psychologiques propres au processus adolescent lui-même. L’adolescence illustrerait ainsi, de manière presque caricaturale, un mécanisme adaptatif continu, qui pourrait nous aider à penser d’autres périodes majeures de changement durant la vie.
Sigmund Freud/Eduard Silberstein : une amitié passionnelle et consanguine
Authors: Houssier Florian 
Published: April 2013

E. Silberstein est l’ami d’adolescence qui a marqué la vie de Freud, à partir des treize ans de ce dernier. Entre 1871 et 1881, la riche correspondance entre eux, fondée essentiellement sur les lettres de Freud, fait ressortir un portrait du jeune Freud ; contrairement à l’idée « officielle » d’une adolescence sans histoire, nous soutenons que cette relation a été marquée par des conflits sexuels intenses et une amitié passionnelle qui s’achèvera, comme bien d’autres amitiés masculines ultérieures, par une rupture du lien.
La formation des enseignants dans l'enseignement catholique avant la création des IUFM
Authors: Poucet Bruno 
Published: April 2013

Entre 1950 et 1970, les établissements de l’enseignement catholique en France tentent d’inventer un système de formation initial de leurs enseignants. Ce système se veut intégral, à savoir qu’il ne sépare pas instruction et éducation, dimension spirituelle et contenu de connaissances. À la différence de l’enseignement public qui a mis en place un système de formation consécutif, dans les établissements privés, le modèle est simultané : formation intellectuelle et formation pédagogique se pratiquent dans un même mouvement. Toutefois, il faut distinguer le niveau primaire du niveau secondaire – dans le premier cas, la formation s’apparente à un engagement religieux, dans le second à l’exercice d’une profession libérale. Bien entendu, un tel système suppose que le public qui fréquente ces institutions partage les mêmes convictions que les enseignants. À partir des années 1950, c’est moins le cas. Une véritable professionnalisation de la formation se met alors en place qui sera profondément bouleversée par le vote de la loi Debré : elle entend en effet transférer aux établissements privés les pratiques de l’enseignement public. Or, ceux-ci résisteront : les véritables transformations se produiront en 1991, lors de la création des IUFM qui met à mal le modèle de formation intégrale pratiqué jusqu’à présent et qui tente de résister en s’accommodant plus ou moins aux nouvelles conditions négociées.