Impact of Composition and Quantity of Triglycerides on Micellarization of Dietary Carotenoids during Simulated Digestion

A carotenoid-rich salad meal with varying amounts of either a structured lipid or dietary oil was digested using simulated gastric and small intestinal conditions. Lutein and carotenes (α-carotene, β-carotene and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (“bioaccessibility”). Relative micellarization was as follows: lutein > α- and β-carotene > lycopene. Micellarization of carotenes, but not lutein, was enhanced (P c8:0 > c4:0). Micellarization efficiency for each carotenoid was similar when equivalent amounts of tri-oleate (c18:1), tri-linoleate (c18:2), and tri-linolenate (c18:3) were added to meal. Relatively low amounts of tri-oleate and canola oil (0.5-1.0%) were required for maximum micellarization of carotenes, but more oil (~2.5%) was required when TG with medium chain saturated fatty acids (e.g., tri-octanoate and coconut oil) was added to salad. The results suggest transfer of carotenoids from chyme to mixed micelles during digestion is inversely correlated with hydrophobicity of the pigment, generally requires minimum (0.5-1%) lipid in the meal, and is influenced by chain length, but not degree of saturation, of dietary fatty acids in TG. (Supported in part by OARDC Graduate Student Scholarship to TH)This research is supported in part by Ohio Agricultural Research and Development Center (OARDC)

Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons.Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT.Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin.Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.peer-reviewe

Colorectal cancer stages transcriptome analysis

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression differences were evaluated across CRC stages using linear regression. Genes with p 0.001 in expression differences were evaluated further in principal component analysis and genes with p 0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10−6 ). Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns

Assessing the reliability of the short form 12 (SF-12) health survey in adults with mental health conditions: a report from the wellness incentive and navigation (WIN) study

Abstract Background Although Short Form (SF)-12 × 2® has been extensively studied and used as a valid measure of health-related quality of life in a variety of population groups, no systematic studies have described the reliability of the measure in patients with behavioral conditions or serious mental illness (SMI). Methods and results We assessed the internal consistency, split-half reliability and annual test-retest correlations in a sample of 1587 participants with either a combination of physical and behavioral conditions or SMI. The Mosier’s alpha was 0.70 for the Physical Composite Scale (PCS) and 0.69 for the Mental Health Composite Scale (MCS), indicating good internal consistency. We observed strong correlations between physical functioning, physical role and body pain scales (r = 0.55–0.56), and between social functioning, emotional role, and mental health (r = 0.53–0.58). We calculated split-half reliabilities to be 0.74 for physical functioning, 0.75 for physical role, 0.73 for emotional role and 0.65 for mental health respectively. We assessed the annual test-retest correlation using intraclass correlation (ICC) and found an ICC of 0.61 for PCS and 0.57 for MCS composite scores, adjusting for age, sex, race/ethnicity, and CRG. We found no decline in the correlations between baseline and the following study years until year 3. Conclusions Our results encourage using SF-12v2® to assess health-related quality of life in the Medicaid population with combined physical and behavioral conditions or similar cohorts. Trial registration The WIN study was registered with clinicaltrials.gov on April 22, 2015. Trial registration number: NCT02440906. Retrospectively registered

Critical Appraisal of Bivalirudin versus Heparin for Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials.

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg

Impact of style of processing on retention and bioaccessibility of β-carotene in cassava (Manihot esculanta

We previously demonstrated that the quantity of -carotene (BC) partitioning in mixed micelles during simulated small intestinal digestion, i.e., the bioaccessibility, of boiled cassava is highly correlated with the BC content of different cultivars. However, cassava is also traditionally prepared by fermentation and roasting. These different methods of preparation have the potential to affect both the retention and bioaccessibility of BC. Here, we first compared retention of BC in boiled cassava, gari (fermentation followed by roasting), and fufu (fermentation followed by sieving and cooking into a paste) prepared from roots of three cultivars. BC content in unprocessed cultivars ranged from 6-8 µg/g wet weight, with cis isomers accounting for approximately one-third of total BC. Apparent retention of BC was approximately 90% for boiled cassava and fufu. In contrast, roasting fermented cassava at 195°C for 20 min to prepare gari decreased BC content by 90%. Retention was increased to 63% when temperature was decreased to 165°C and roasting was limited to 10 min. Processing was also associated with a decline in all-trans-BC and concomitant increase in 13-cis-BC. The efficiency of micellarization of all-trans and cis isomers of BC during simulated digestion was 25-30% for boiled cassava and gari and independent of cultivar. However, micellarization of BC isomers during digestion of fufu was only 12-15% (P &lt; 0.05). These differences in retention and bioaccessibility of BC from cassava products prepared according to traditional processing methods suggest that gari and fufu may provide less retinol activity equivalents than isocaloric intake of boiled cassava

Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma

International audienceBackground The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. Methods F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14 days later, either CDDP or carboplatin was administered i.c. by CED, followed 24h later by radiotherapy using either a synchro- tron or, subsequently, megavoltage linear accelerators (LINAC). Results CDDP was administered at a dose of 3 µg in 5 µL, followed 24h later with an irradiation dose of 15 Gy or carbopl- atin at a dose of 20 µg in 10 µL, followed 24h later with 3 fractions of 8 Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180 days with 33% long term survivors (LTS) for CDDP and a MeST > 60 days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72 µg of carboplatin administered by means of Alzet® osmotic pumps over 7 days. This resulted in a MeST of > 180 days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. Conclusions The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promis- ing survival data ever reported using the F98 glioma model