Severe Cerebral Venous and Sinus Thrombosis: Clinical Course, Imaging Correlates, and Prognosis.

BACKGROUND: Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically. METHODS: Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up. RESULTS: 114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1). CONCLUSION: The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.

EcoCyc: fusing model organism databases with systems biology.

EcoCyc (http://EcoCyc.org) is a model organism database built on the genome sequence of Escherichia coli K-12 MG1655. Expert manual curation of the functions of individual E. coli gene products in EcoCyc has been based on information found in the experimental literature for E. coli K-12-derived strains. Updates to EcoCyc content continue to improve the comprehensive picture of E. coli biology. The utility of EcoCyc is enhanced by new tools available on the EcoCyc web site, and the development of EcoCyc as a teaching tool is increasing the impact of the knowledge collected in EcoCyc.

RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more.

This article summarizes our progress with RegulonDB (http://regulondb.ccg.unam.mx/) during the past 2 years. We have kept up-to-date the knowledge from the published literature regarding transcriptional regulation in Escherichia coli K-12. We have maintained and expanded our curation efforts to improve the breadth and quality of the encoded experimental knowledge, and we have implemented criteria for the quality of our computational predictions. Regulatory phrases now provide high-level descriptions of regulatory regions. We expanded the assignment of quality to various sources of evidence, particularly for knowledge generated through high-throughput (HT) technology. Based on our analysis of most relevant methods, we defined rules for determining the quality of evidence when multiple independent sources support an entry. With this latest release of RegulonDB, we present a new highly reliable larger collection of transcription start sites, a result of our experimental HT genome-wide efforts. These improvements, together with several novel enhancements (the tracks display, uploading format and curational guidelines), address the challenges of incorporating HT-generated knowledge into RegulonDB. Information on the evolutionary conservation of regulatory elements is also available now. Altogether, RegulonDB version 8.0 is a much better home for integrating knowledge on gene regulation from the sources of information currently available.

Inhomogeneous Longitudinal Cardiac Rotation and Impaired Left Ventricular Longitudinal Strain in Children and Young Adults with End-Stage Renal Failure Undergoing Hemodialysis.

BACKGROUND: Cardiac dysfunction frequently complicates the clinical course of patients with end-stage renal failure (ESRF). Recently, we observed abnormal longitudinal cardiac rotation (LR) among patients with ESRF. In this study, we sought to quantify LR mechanics in patients undergoing hemodialysis (HD). METHODS: Twenty-four subjects, 12 ESRF patients (58% male; age 17.5 ± 4.4 years) receiving HD, and 12 aged-matched controls, were prospectively studied. Patients underwent echocardiographic studies before and after HD. LR mechanics were quantified with two-dimensional speckle tracking echocardiography. Peak systolic left ventricular (LV) longitudinal strain and displacement measurements were obtained in all subjects. RESULTS: LR mechanics were successfully quantified in all subjects using 5 key echocardiographic features of LR. We identified two different inhomogeneous LR motion patterns in 41.7% of ESRF patients, characterized by a delayed timing of LR or increased segmental apical rotation. Inhomogeneous LR patterns were not found in controls. Timing of early-systolic counterclockwise LR increased after HD (P = 0.006). In patients, late-systolic clockwise LR occurred earlier (P = 0.043), and showed a significant prolongation after HD (P = 0.003). Longitudinal strain was significantly impaired in patients (P = 0.015), and further decreased after HD (P < 0.0001). Strong correlations were observed between strain and displacement parameters and LR mechanics. CONCLUSIONS: Quantifying LR using speckle tracking echocardiography was feasible, easy, and reproducible. Inhomogeneous LR motion patterns were demonstrated in a large proportion of patients with ESRF. LV dysfunction seems the most important determinant of inhomogeneous LR. Further studies are required to validate these findings.

Quality-of-life in patients with post-traumatic hypopituitarism.

PRIMARY OBJECTIVE: Hypopituitarism is a frequent complication in patients after traumatic brain injury (TBI). Both TBI and hypopituitarism can lead to complex cognitive and affective deficits. This study was intended to examine the quality-of-life in patients with post-traumatic hypopituitarism (PTH) and to discern the effect of this endocrinological disorder on general outcome of patients after TBI including earning capacity. Research type: Retrospective analysis of clinical data. METHODS AND PROCEDURES: Ninety-seven symptomatic patients were screened after TBI for PTH. Their results were examined in the SF-36 [a standardized questionnaire for quality of life (QoL)] comparing the groups with or without PTH. After 6 months of hormone substitution (if necessary), patients were asked to repeat the SF-36. MAIN OUTCOMES AND RESULTS: Forty-six patients were diagnosed with PTH (47.5%). All patients included had a significantly lower QoL compared to the standard population. QoL was significantly worse in patients with PTH. There was no significant difference with regard to earning capacity. After hormone substitution, patients achieved better SF-36-results, albeit the difference was lacking statistical significance. CONCLUSIONS: PTH is frequent after TBI. PTH turns out to further diminish QoL, without affecting earning capacity. Hormone substitution might improve QoL in patients with PTH, but future research is needed to confirm this hypothesis.

RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units).

RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database of the best-known regulatory network of any free-living organism, that of Escherichia coli K-12. The major conceptual change since 3 years ago is an expanded biological context so that transcriptional regulation is now part of a unit that initiates with the signal and continues with the signal transduction to the core of regulation, modifying expression of the affected target genes responsible for the response. We call these genetic sensory response units, or Gensor Units. We have initiated their high-level curation, with graphic maps and superreactions with links to other databases. Additional connectivity uses expandable submaps. RegulonDB has summaries for every transcription factor (TF) and TF-binding sites with internal symmetry. Several DNA-binding motifs and their sizes have been redefined and relocated. In addition to data from the literature, we have incorporated our own information on transcription start sites (TSSs) and transcriptional units (TUs), obtained by using high-throughput whole-genome sequencing technologies. A new portable drawing tool for genomic features is also now available, as well as new ways to download the data, including web services, files for several relational database manager systems and text files including BioPAX format.

Formation of structured polygonal nanoparticles by phase-separated comb-like polymers.

A simple approach using comb-like polymers that undergo nanophase separation between the polyester backbone and the stearoyl side chains is proposed for the preparation of structured non-spherical nanoparticles from a nanoemulsion. Depending on the degree of esterification of the OH groups of poly(glycerol adipate) differently ordered nanostructures is obtained. A perfect lamellar arrangement is obtained for polymers with a high degree of esterification and leads to spherical nanoparticles with an internal onion-like structure. However, when the degree of esterification is only 20 mol%, polygonal nanoparticles with an internal pseudo-hexagonal structure are obtained. The differences in the nanoparticle shapes are related to the volume fraction of the paraffinic pool.

Intended and Unintended Targeting of Polymeric Nanocarriers: The Case of Modified Poly(glycerol adipate) Nanoparticles.

Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate) (PGAS) are promising carriers for drug delivery. In order to investigate the impact of the particle interface characteristics on the biological fate, PGAS nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have similar particle sizes, but less negative zeta-potentials. Nanoparticles are double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676 (covalently bound to HPMA copolymer), and their biodistribution is investigated noninvasively by multispectral optical imaging. Both covalent and noncovalent coatings cause changes in the pharmacokinetics and biodistribution in healthy and tumor-bearing mice. In addition to the intended tumor accumulation, high signals of both fluorescent dyes are also observed in other organs, including liver, ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers needs further detailed and systematic investigations, especially with respect to the observed ovarian and adrenal gland accumulation.

Sociocultural Influence on Obesity and Lifestyle in Children: A Study of Daily Activities, Leisure Time Behavior, Motor Skills, and Weight Status.

BACKGROUND: Juvenile overweight is increasing, and effective preventive measures are needed. After years of arbitrarily assigning these measures disregarding socioeconomic and/or cultural differences, it has become necessary to tailor interventions more specific to these target groups. Providing data for such an intervention is the objective of this study. METHODS: Influencing variables on children's weight status, motor skills and lifestyle have been analyzed among 997 first graders (53.2% male) involved in the Children's Health InterventionaL Trial (CHILT). RESULTS: Median age was 6.9 years; 7.3% were obese, 8.8% were overweight. Children with low socioeconomic status (SES) were more likely to be obese (p = 0.029). Low SES (p ˂ 0.001), migration background (p = 0.001) and low sports activity levels (p = 0.007) contributed most to an increased consumption of television. Migration background (p = 0.003) and male gender (p < 0.001) were the strongest factors in predicting a greater consumption of computer/video games. Children with higher SES (p = 0.02), lower BMI (p = 0.035), and males (p = 0.001) performed better in motor tests. CONCLUSION: Children with a low SES and migration background were more likely to exhibit unfavorable health behavior patterns, higher BMI scores, and poorer motor skills. Interventions should integrate motivational and targeting strategies and consider cultural and educational differences to address these vulnerable groups.

Investigating Respondents and Nonrespondents of a Postal Breast Cancer Questionnaire Survey Regarding Differences in Age, Medical Conditions, and Therapy.

BACKGROUND: Collecting patient-reported data via postal questionnaires is a common and frequently used technique. Selection bias may occur through lost data from nonrespondents. This study investigated differences in characteristics between respondents and nonrespondents of a postal breast cancer survey. PATIENTS AND METHODS: The investigation was based on a cross-sectional postal questionnaire survey for the mandatory annual routine (re-)certification of accredited breast centers in North Rhine-Westphalia in 2010. Out of 4,444 patients meeting the inclusion criteria who gave their consent to participate, 3,856 respondents sent back a questionnaire and 588 nonrespondents did not. Using logistic regression, differences between respondents and nonrespondents regarding information gathered through hospital staff concerning age, affected breast, UICC (Union for International Cancer Control) staging and grading, ASA (American Society of Anesthesiologists) classification, neoadjuvant chemotherapy, and type of surgery were assessed. RESULTS: Very young and very old patients sent back their questionnaire significantly less frequently, as did patients who showed a later cancer stage and poorer general health and those who underwent mastectomy. CONCLUSION: Differences exist between respondents and nonrespondents with regard to age, disease, and therapy characteristics that need to be considered for the interpretation and generalizability of survey results due to selection bias.

Quality of Basic Life Support - A Comparison between Medical Students and Paramedics.

INTRODUCTION: Poor survival rates after cardiac arrest can partly be explained by poor basic life support skills in medical professionals. AIM: This study aimed to assess quality of basic life support in medical students and paramedics. MATERIALS AND METHODS: We conducted a prospective observational study with 100 early medical students (group A), 100 late medical students (group B) and 100 paramedics (group C), performing a 20-minute basic life support simulation in teams of two. Average frequency and absolute number of chest compressions per minute (mean (±SD)), chest decompression (millimetres of compression remaining, mean (±SD)), hands-off-time (seconds/minute, mean (±SD)), frequency of switching positions between ventilation and chest compression (per 20 minutes) and rate of sufficient compressions (depth ≥50mm) were assessed as quality parameters of CPR. RESULTS: In groups A, B and C the rates of sufficiently deep chest compressions were 56%, 42% and 52%, respectively, without significant differences. Male gender and real-life CPR experience were significantly associated with deeper chest compression. Frequency and number of chest compressions were within recommended goals in at least 96% of all groups. Remaining chest compressions were 6 mm (±2), 6 mm (±2) and 5 mm (±2) with a significant difference between group A and C (p=0.017). Hands-off times were 6s/min (±1), 5s/min (±1) and 4s/min (±1), which was significantly different across all three groups. CONCLUSION: Overall, paramedics tended to show better quality of CPR compared to medical students. Though, chest compression depth as an important quality characteristic of CPR was insufficient in almost 50% of participants, even in well trained paramedics. Therefore, we suggest that an effort should be made to find better ways to educate health care professionals in BLS.

Frey's syndrome after superficial parotidectomy: role of the sternocleidomastoid muscle flap: a prospective nonrandomized controlled trial.

BACKGROUND: The prevalence of Frey's syndrome (FS) after superficial parotidectomy in correlation to the sternocleidomastoid muscle flap (SCMMF) interposition is analyzed. METHODS: A prospective nonrandomized controlled multicenter trial included 130 patients. During superficial parotidectomy, SCMMF was dissected, if excised specimens' volume exceeded 25 mL (SCMMF group). Follow-up examinations took place after 6, 12, and 24 months and included a Minor's test. RESULTS: SCMMF was dissected in 30 (23.1%) patients. A total of 104, 80, and 68 patients completed the 1st, 2nd, and the 3rd follow-up, respectively. FS was detectable with nonvarying prevalence (46.3%, 45.6%, and 43.4%, respectively) during follow-up. The prevalence was higher in the SCMMF group (59.9%) than in the non-SCMMF group (41.8%; P = .92). The sweating area increased during follow-up (P = .12). Overall, 89.5% of patients characterized FS as not disturbing after 2 years. CONCLUSIONS: FS occurred with a steady and high prevalence after superficial parotidectomy. In particular, SCMMF did not lower the risk of FS.

Cytokine and Chemokine Signature in Elite Versus Viremic Controllers Infected with HIV.

HIV long-term nonprogressors (LTNPs) maintaining high CD4(+) T-cell counts without antiretroviral therapy (ART) are divided into elite controllers (ECs) with undetectable and viremic controllers (VCs) with low viral loads. Little is known about the long-term changes of T-cell subsets and inflammation patterns in ECs versus VCs. The aim of the study was to explore the long-term evolution of CD4(+) T-cell levels in LTNPs and to analyze cytokine profiles in ECs versus VCs. Nineteen ECs and 15 VCs were enrolled from the natural virus controller cohort (NaViC). T-cell counts were monitored over years, the mean annual change was calculated, and plasma concentrations of 25 cytokines were evaluated using a multiplex bead array. While absolute numbers of T cells did not differ between ECs and VCs over time, we observed a significant decrease of CD4(+) T-cell percentages in VCs, but not in ECs (median [interquartile range]: ECs: 37% [28-41] vs. VCs: 29% [25-34]; p = .02). ECs had lower levels of macrophage inflammatory protein-1ß (MIP-1ß, p = .003), interferon γ-induced protein-10 (IP-10, p = .03), and monokine induced by interferon-γ (MIG, p = .02). CD4(+) T-cell percentages inversely correlated with MIP 1-ß (r = -0.42, p = .017) and IP-10 (r = -0.77, p < .0001). A subtle decline of CD4(+) T-cell percentages could be observed in VCs, but not in ECs, which was associated with higher plasma levels of proinflammatory cytokines. Hence, even low levels of HIV replication might go along with a progressive decline in CD4(+) T-cell counts in LTNPs.

A novel nonparametric measure of explained variation for survival data with an easy graphical interpretation.

INTRODUCTION: For survival data the coefficient of determination cannot be used to describe how good a model fits to the data. Therefore, several measures of explained variation for survival data have been proposed in recent years. METHODS: We analyse an existing measure of explained variation with regard to minimisation aspects and demonstrate that these are not fulfilled for the measure. RESULTS: In analogy to the least squares method from linear regression analysis we develop a novel measure for categorical covariates which is based only on the Kaplan-Meier estimator. Hence, the novel measure is a completely nonparametric measure with an easy graphical interpretation. For the novel measure different weighting possibilities are available and a statistical test of significance can be performed. Eventually, we apply the novel measure and further measures of explained variation to a dataset comprising persons with a histopathological papillary thyroid carcinoma. CONCLUSION: We propose a novel measure of explained variation with a comprehensible derivation as well as a graphical interpretation, which may be used in further analyses with survival data.

Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.

BACKGROUND: Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). METHODS/DESIGN: The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. DISCUSSION: The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. TRIAL REGISTRATION: ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

Low-grade proteinuria is highly prevalent in HIV-positive patients on antiretroviral treatment.

OBJECTIVES: HIV-positive patients are at an increased risk for chronic kidney disease. However, these data mainly derive from cohorts with a high percentage of African-American patients, representing a specific ethnical risk group for chronic kidney disease. The aim of this study was to estimate the prevalence and risk factors specifically for early signs of kidney dysfunction in a large, predominantly white cohort of HIV patients. DESIGN: Cross-sectional study. METHODS: Prevalence of low-grade proteinuria was measured by quantitative analysis of urinary protein-to-creatinine ratio (cutoff >70 mg/g) and further differentiated by assessing α1-microglobulin (tubular proteinuria) and albumin-to-creatinine ratio (glomerular proteinuria) of HIV patients attending the University Hospital in Cologne, Germany. Together with standard and HIV-related laboratory findings and medical history, risk factors for each form of proteinuria were identified using multivariate forward selection. RESULTS: Of 945 enrolled patients, 55% were identified with low-grade proteinuria, 41% with tubular proteinuria, and 20% with glomerular proteinuria. Older age was a risk factor for all forms of proteinuria in multivariate analysis. Low-grade proteinuria was also associated with concomitant diabetes and exposure to nucleoside reverse transcriptase inhibitor [anytime during HIV infection, not tenofovir (TDF)-specific], whereas tubular proteinuria was linked to current and any exposure to nucleoside reverse transcriptase inhibitor (TDF-specific). Further risk factors for glomerular proteinuria were hypertension and diabetes in this cohort. CONCLUSION: Low-grade, glomerular and tubular proteinuria are highly prevalent in this large white HIV cohort. Older age represents a nonmodifiable risk factor for all forms of proteinuria. Glomerular proteinuria is associated with modifiable cardiovascular, but not HIV-related risk factors, whereas tubular proteinuria is linked to TDF exposure.

Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies.

OBJECTIVES: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. METHODS: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. RESULTS: The median age of participants was 64 years (interquartile range 50-75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). CONCLUSION: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.

The EcoCyc Database.

EcoCyc is a bioinformatics database available at EcoCyc.org that describes the genome and the biochemical machinery of Escherichia coli K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the E. coli cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of E. coli. EcoCyc is an electronic reference source for E. coli biologists and for biologists who work with related microorganisms. The database includes information pages on each E. coli gene, metabolite, reaction, operon, and metabolic pathway. The database also includes information on E. coli gene essentiality and on nutrient conditions that do or do not support the growth of E. coli. The website and downloadable software contain tools for analysis of high-throughput data sets. In addition, a steady-state metabolic flux model is generated from each new version of EcoCyc. The model can predict metabolic flux rates, nutrient uptake rates, and growth rates for different gene knockouts and nutrient conditions. This review provides a detailed description of the data content of EcoCyc and of the procedures by which this content is generated.

Evidence classification of high-throughput protocols and confidence integration in RegulonDB.

RegulonDB provides curated information on the transcriptional regulatory network of Escherichia coli and contains both experimental data and computationally predicted objects. To account for the heterogeneity of these data, we introduced in version 6.0, a two-tier rating system for the strength of evidence, classifying evidence as either 'weak' or 'strong' (Gama-Castro,S., Jimenez-Jacinto,V., Peralta-Gil,M. et al. RegulonDB (Version 6.0): gene regulation model of Escherichia Coli K-12 beyond transcription, active (experimental) annotated promoters and textpresso navigation. Nucleic Acids Res., 2008;36:D120-D124.). We now add to our classification scheme the classification of high-throughput evidence, including chromatin immunoprecipitation (ChIP) and RNA-seq technologies. To integrate these data into RegulonDB, we present two strategies for the evaluation of confidence, statistical validation and independent cross-validation. Statistical validation involves verification of ChIP data for transcription factor-binding sites, using tools for motif discovery and quality assessment of the discovered matrices. Independent cross-validation combines independent evidence with the intention to mutually exclude false positives. Both statistical validation and cross-validation allow to upgrade subsets of data that are supported by weak evidence to a higher confidence level. Likewise, cross-validation of strong confidence data extends our two-tier rating system to a three-tier system by introducing a third confidence score 'confirmed'. Database URL: http://regulondb.ccg.unam.mx/

In vitro toxicity of Stearoyl-poly(glycerol adipate) nanoparticles.

PURPOSE: Poly(glycerol adipate) (PGA)-based nanoparticles are promising carriers for drug delivery with a wide range of available structures. The biodegradable polymer with pendant free hydroxyl groups can be diversely functionalized. In this study, the toxicity of different Stearoyl-PGA nanoparticles with respect to erythrocytes and HepG2 cells was assessed. These cells are crucial test systems for intravenously injected biomedical particles. METHODS: For this work, a series of PGA polyesters with 0, 20, 50 and 65 mol% of converted hydroxyl groups was synthesized with stearic acid (PGABB, S20, S50, S65). Nanoparticles were prepared with these polymers by an optimized nanoprecipitation method. Physicochemical characterization was performed by photon correlation spectroscopy and zeta potential measurement. Cell compatibility was studied by a hemolysis assay with separated red blood cells as well as a QBlue viability test and a modified LDH cytotoxicity assay with HepG2 cells. RESULTS AND CONCLUSIONS: Different self-stabilizing nanoparticles with narrow size distributions in the range of 100-140 nm were prepared. All tested nanoparticle samples were nontoxic for HepG2 cells. In fact, increased metabolic activity and proliferation was observed after 24 h incubation with the Stearoyl-PGA particles. Apart from PGAS20, all samples did not show any hemolytic effect. Hemolysis of PGAS20 particles could be considerably decreased by adding Poloxamer 188 during the preparation process.