Background: To determine the correlation between obesity in school-aged children and imbalance of gut microbes by examining the ratio change of intestinal Bifidobacteria and E.coli in obese children compared to non-obese controls. Methods: A hospital-based 1:1 case–control study was performed. Fecal samples of the subjects were collected for DNA extraction and analyzed by quantitative real-time PCR (qPCR) to determine the copy number of Bifidobacteria and E.coli. The ratio of two microbes (B/E) was then calculated and statistically analyzed. Results: Subjects of the obesity group and control group showed no significant difference in age, gender or height (P > 0.05); whereas they had significant differences in body weight and BMI. Copy numbers of Bifidobacteria and E.coli per gram of wet fecal samples were first determined using qPCR in both obese and normal groups, which were further used for the calculation of B/E ratio. We found that B/E ration in the two groups showed significant difference (P < 0.05). Corrected χ2 test was performed for the two groups against B/E < 1, and it was found that there was a positive correlation (OR = 719.2, OR 95% C.I. = 81.57-6341.18) between B/E ratio decrease with childhood obesity. Conclusions: The obese children have a lower amount of Bifidobacteria and higher amount of E.coli (smaller B/E ratio) compared to normal non-obese children. It was suggested that obesity in children may be associated with the imbalance of gut microbes.
Background: The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12–14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear. Results: Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin’s cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death. Conclusions: Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.
Background: The Democratic Republic of the Congo (DRC) has the highest number of severe malaria cases in the world. In early 2012, the National Malaria Control Programme (NMCP) changed the policy for treating severe malaria in children and adults from injectable quinine to injectable artesunate. To inform the scaling up of injectable artesunate nationwide, operational research is needed to identify constraints and challenges in the DRC’s specific setting. Methods: The implementation of injectable quinine treatment in 350 patients aged 2 months or older in eight health facilities from October 2012 to January 2013 and injectable artesunate in 399 patients in the same facilities from April to June 2013 was compared. Since this was an implementation study, concurrent randomized controls were not possible. Four key components were evaluated during each phase: 1) clinical assessment, 2) time and motion, 3) feasibility and acceptability, and 4) financial cost. Results: The time to discharge was lower in the artesunate (median = 2, 90 % central range 1–9) compared to the quinine group (3 (1–9) days; p <0.001). Similarly, the interval between admission and the start of intravenous (IV) treatment (2 (0–15) compared to 3 (0–20) hours; p <0.001) and parasite clearance time (23 (11–49) compared to 24 (10–82) hours; p <0.001) were lower in the artesunate group. The overall staff pre-administration time (13 (6–38) compared to 20 (7–50) minutes; p <0.001) and the personnel time spent on patient management (9 (1–24) compared to 12 (3–52) minutes; p <0.001) were lower in the artesunate group. In hospitals and health centres, the mean (standard deviation, SD) total cost per patient treated for severe malaria with injectable artesunate was USD 51.94 (16.20) and 19.51 (9.58); and USD 60.35 (17.73) and 20.36 (6.80) with injectable quinine. Conclusions: This study demonstrates that injectable artesunate in the DRC is easier to use and it costs less than injectable quinine. These findings provide the basis for practical recommendations for rapid national deployment of injectable artesunate in the DRC.
Background: The influence of diabetes mellitus (DM) on platelet reactivity (PR) in prasugrel or ticagrelor treated patients is not well studied. Methods: In an observational study involving 777 patients with acute coronary syndrome undergoing percutaneous coronary intervention treated by either prasugrel 10 mg od (n = 315) or ticagrelor 90 mg bid (n = 462), platelet function was assessed using the VerifyNow P2Y12 function assay (in PRU) at one month post intervention. Results: In the overall population, ticagrelor and insulin-treated DM affected PR, with a decrease in log by 0.88 (corresponding to a 58 % decrease in PR) compared to prasugrel-treated patients (p < 0.001), and an increase in log by 0.26 (corresponding to a 30 % increase in PR) compared to non-diabetic patients (p = 0.01), respectively. PR in prasugrel-treated patients differed significantly by DM status: 70.0 (36.3-113.0) in non-diabetic vs 69.0 (44.5-115.3) in non insulin-treated diabetic vs 122.0 (69.0-161.0) in insulin-treated diabetic patients, p for trend = 0.01. No differences were observed in ticagrelor-treated patients. By multivariate analysis, in prasugrel-treated patients insulin-treated DM was the only factor predicting PR, with log of PR increased by 0.42 (corresponding to a 52 % increase in PR) compared to non-diabetic patients (p = 0.001). No factor was found to affect PR in ticagrelor-treated patients. Conclusions: Patients with insulin-treated DM treated with prasugrel post PCI have higher PR, than patients without DM or non insulin-treated diabetic patients treated with this drug. Ticagrelor treated patients have overall lower PR than patients on prasugrel, independent of DM status or insulin treatment.Trial registrationClinical Trials Gov. NCT01774955
Background: Low circulating levels of total vitamin D [25(OH)D and 25(OH)D3] have been associated with vascular complications in few studies on individuals with type 1 diabetes. However, these measures are affected by UV light exposure. Circulating 25(OH)D2, however, solely represents dietary intake of vitamin D2, but its association with complications of diabetes is currently unknown. We investigated the associations between 25(OH)D2 and 25(OH)D3 and the prevalence of albuminuria, retinopathy and cardiovascular disease (CVD) in individuals with type 1 diabetes. Methods: We measured circulating 25(OH)D2 and 25(OH)D3 in 532 individuals (40 ± 10 years old, 51 % men) with type 1 diabetes who participated in the EURODIAB Prospective Complications Study. Cross-sectional associations of 25(OH)D2 and 25(OH)D3 with albuminuria, retinopathy and CVD were assessed with multiple logistic regression analyses adjusted for age, sex, season, BMI, smoking, HbA1c, total-HDL-cholesterol-ratio, systolic blood pressure, antihypertensive medication, eGFR, physical activity, alcohol intake, albuminuria, retinopathy and CVD, as appropriate. Results: Fully adjusted models revealed that 1 nmol/L higher 25(OH)D2 and 10 nmol/L higher 25(OH)D3 were associated with lower prevalence of macroalbuminuria with ORs (95 % CI) of 0.56 (0.43;0.74) and 0.82 (0.72;0.94), respectively. These vitamin D species were not independently associated with microalbuminuria, non-proliferative and proliferative retinopathy or CVD. Conclusions: In individuals with type 1 diabetes, both higher 25(OH)D2 and 25(OH)D3 are associated with a lower prevalence of macroalbuminuria, but not of retinopathy and CVD. Prospective studies are needed to further examine the associations between 25(OH)D2 and 25(OH)D3 and the development of microvascular complications and CVD in type 1 diabetes.
Background: The objective of this study was to evaluate a novel prostate endorectal immobilization system (EIS) for improving the delivery of hypofractionated Stereotactic Ablative Body Radiotherapy (SABR) for prostate cancer. Methods: Twenty patients (n = 20) with low- or intermediate-risk prostate cancer (T1-T2b, Gleason Score < 7, PSA ≤ 20 ng/mL), were treated with an EIS in place using Volumetric Modulated Arc Therapy (VMAT), to a prescription dose of 26 Gy delivered in 2 fractions once per week; the intent of the institutional clinical trial was an attempt to replicate brachytherapy-like dosimetry using SABR. EBT3 radiochromic film embedded within the EIS was used as a quality assurance measure of the delivered dose; additionally, prostate intrafraction motion captured using pre- and post-treatment conebeam computed tomography (CBCT) scans was evaluated. Treatment plans were generated for patients with- and without the EIS to evaluate its effects on target and rectal dosimetry. Results: None of the observed 3-dimensional prostate displacements were ≥ 3 mm over the elapsed treatment time. A Gamma passing rate of 95.64 ± 4.28 % was observed between planned and delivered dose profiles on EBT3 film analysis in the low-dose region. No statistically significant differences between treatment plans with- and without-EIS were observed for rectal, bladder, clinical target volume (CTV), and PTV contours (p = 0.477, 0.484, 0.487, and 0.487, respectively). A mean rectal V80% of 1.07 cc was achieved for plans using the EIS. Conclusions: The EIS enables the safe delivery of brachytherapy-like SABR plans to the prostate while having minimal impact on treatment planning and rectal dosimetry. Consistent and reproducible immobilization of the prostate is possible throughout the duration of these treatments using such a device.
Background: Common genetic variants have been shown to modify BRCA1 penetrance. The aim of this study was to validate these reports in a special cohort of Norwegian BRCA1 mutation carriers that were selected for their extreme age of onset of disease. Methods: The ten variants rs13387042, rs3803662, rs8170, rs9397435, rs700518, rs10046, rs3834129, rs1045485, rs2363956 and rs16942 were selected to be tested on samples from our biobank. We selected female BRCA1 mutation carriers having had a diagnosis of breast or ovarian cancer below 40 years of age (young cancer group, N = 40), and mutation carriers having had neither breast nor ovarian cancer above 60 years of age (i.e., old no cancer group, N = 38). Relative risks and odd ratios of belonging to the young cancer versus old no cancer groups were calculated as a function of having or not having the SNPs in question. Results: Five of the ten variants were found to be significantly associated with early onset cancer. Some of the variation between our results and those previously reported may be ascribed to stochastic effects in our limited number of patient studies, and/or genetic drift in linkage disequilibrium in the genetically isolated Norwegian population. This is in accordance with the understanding that the SNPs are markers in linkage disequilibrium with their respective disease-causing genetic variants, and that this may vary between different populations. Conclusions: The results confirmed associations previously reported, with the notion that the degree of association may differ between other populations, which must be considered when discussing the clinical use of the associations described.
Background: The results of several papers have confirmed the existence of correlations between an unhealthy diet and the presence of metabolic syndrome. However, relationships between eating habits and metabolic obesity with normal weight have not yet been sufficiently studied. The aim of the study is to determine which dietary patterns are present in individuals with a normal BMI and to find out whether those patterns were connected with the risk of metabolic syndrome and its features. Methods: A cross-sectional study was carried out in a group of 2479 subjects with a normal weight (BMI = 18.5–24.9 kg/m2), aged between 37–66. The study included the evaluation of eating habits, anthropometric measurements, blood pressure tests and the analysis of the collected fasting-blood samples, on the basis of which cholesterol, triglycerides and glucose levels were determined. Dietary patterns were determined by means of factor analysis. Results: In the group of individuals with a normal BMI, four dietary patterns were distinguished: “healthy”, “fat, meat and alcohol”, “prudent” and “coca cola, hard cheese and French fries”. After controlling for potential confounders, subjects in the highest tertile of prudent dietary pattern scores had a lower odds ratio for the metabolic obesity normal weight) (odds ratio: 0.69; 95 % CI: 0.53-0.89; p < 0.01) and low HDL cholesterol (odds ratio: 0.77; 95 % CI: 0.59-0.99; p < 0.05), in comparison to those from the lowest tertile, whereas the individuals in the second tertile had a higher odds ratio for the increased blood glucose concentration than those in the lowest tertile (odds ratio: 0.74; 95 % CI: 0.57-0.96; p < 0.05). Conclusion: A dietary pattern characterized by a high consumption of fish and whole grains, and a low consumption of refined grains, sugar, sweets and cold cured meat, is connected with lower risk of metabolic obesity normal weight as well as with the lower risk of low HDL cholesterol concentration and increased glucose concentration.
Background: Microalgae have recently been attracting attention as a potential platform for the production of biofuels. Euglena gracilis, a unicellular phytoflagellate, has been proposed as an attractive feedstock to produce biodiesel because it can produce large amounts of wax esters, consisting of medium-chain fatty acids and alcohols with 14:0 carbon chains. E. gracilis cells highly accumulate a storage polysaccharide, a β-1,3-glucan known as paramylon, under aerobic conditions. When grown aerobically and then transferred into anaerobic conditions, E. gracilis cells degrade paramylon to actively synthesize and accumulate wax esters. Thus, the enhanced accumulation of paramylon through the genetic engineering of photosynthesis should increase the capacity for wax ester production. Results: We herein generated transgenic Euglena (EpFS) cells expressing the cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), which is involved in the Calvin cycle, to enhance its photosynthetic activity. FBP/SBPase was successfully expressed within Euglena chloroplasts. The cell volume of the EpFS4 cell line was significantly larger than that of wild-type cells under normal growth conditions. The photosynthetic activity of EpFS4 cells was significantly higher than that of wild type under high light and high CO2, resulting in enhanced biomass production, and the accumulation of paramylon was increased in transgenic cell lines than in wild-type cells. Furthermore, when EpFS cell lines grown under high light and high CO2 were placed on anaerobiosis, the productivity of wax esters was approximately 13- to 100-fold higher in EpFS cell lines than in wild-type cells. Conclusion: Our results obtained here indicate that the efficiency of biomass production in E. gracilis can be improved by genetically modulating photosynthetic capacity, resulting in the enhanced production of wax esters. This is the first step toward the utilization of E. gracilis as a sustainable source for biofuel production under photoautotrophic cultivation.
Background: Although a growing body of evidence suggests that low dead space syringes may reduce the risk of human immunodeficiency virus (HIV) and Hepatitis C virus infection associated with sharing syringes among people who inject drugs, there is little evidence of effective approaches to motivate people who inject drugs (PWID) to shift from high to low dead space syringes. Methods: Using a mix of consumer and trade marketing approaches, informed by rapid assessments of both the syringe market and PWID preferences, practices, and behaviors in Hanoi and Ho Chi Minh City, Population Services International (PSI) Vietnam piloted an intervention to increase the use of low dead space syringes (LDSS) in the three provinces of Hanoi, Ho Chi Minh City, and Thai Nguyen, where an estimated 31 % of PWID are HIV positive and 58 % are living with hepatitis C virus (HCV). Results: This paper provides a summary of the social marketing activities implemented and results achieved by PSI Vietnam during an initial 1-year pilot period from December 2012 to December 2013 in these three provinces to explore their effectiveness in motivating PWID to use low dead space syringes.We found major increases in sales of LDSS accompanied by increases in reported use and consistent use of LDSS among PWID in the three provinces included in the pilot program and a positive and independent association (odds ratio (OR) 21.08; 95 % confidence interval (CI) 10.6–27.3) between LDSS use and exposure to social marketing activities. We also found that LDSS use had a stronger association with perceptions of LDSS product quality than with perceptions regarding LDSS potential to reduce HIV transmission risk and use. Conclusions: We conclude that social marketing interventions have an important role to play in widening access to and the use of LDSS for PWID, as they address the need for PWID to find LDSS when and where they need them and also promote the benefits of LDSS use to PWID. High coverage of these activities among PWID appears to be the key in achieving these successes.