Monodisperse magnetic lecithin-PFP submicron bubbles as dual imaging contrast agents for ultrasound (US) and MRI

Multimodal imaging is a recent idea of combining two or more imaging methods synergistically to overcome the weakness of individual imaging modalities and utilizing complementary benefits. Ultrasound (US) and magnetic resonance imaging (MRI) are widely used imaging techniques in healthcare and to fully utilize the potential of fusion imaging, dual-modal contrast agents are necessary to improve disease diagnosis by enhancing contrast resolution and reducing health risks associated with the dual dosage of contrast agents. In this study, magnetic microbubbles were synthesized by incorporating oleic acid stabilized superparamagnetic iron oxide nanoparticles (OA-SPIONs) into lecithin microbubbles, encapsulating the perfluoropentane (PFP) core. The magnetic microbubbles were characterized by FTIR, SEM, MFM, zeta potential, in vitro MRI, and ultrasound. Upon in vitro MRI, magnetic microbubbles showed a negative contrast effect by producing darker T2 weighted images. Magnetic microbubbles showed concentration-dependent response with a decrease in signal intensity with an increase in the concentration of OA-IONP in microbubbles. However, a decrease in acoustic enhancement was also observed with an increase in OA-IONP concentration, therefore concentration was optimized to achieve the best effect on both modalities. The magnetic lecithin microbubble with 10 mg SPIONs provided the best contrast on both US and MR imaging. The hemocompatibility testing resulted in hemolysis less than 7% with plasma recalcification time and thrombin time of 240 s and 6 s corresponding to excellent hemocompatibility. Thus the magnetic microbubbles with a phase convertible PFP core encapsulated by a lecithin shell loaded with OA-SPIONs can serve as a potential bimodal contrast agent for both US and MRI imaging.

The magnetic microbubbles with phase convertible PFP core encapsulated by lecithin shell loaded with OA-SPIONs can serve as a potential bimodal contrast agent for both ultrasound (US) and magnetic resonance imaging (MRI).     

Migraine,inflammatory bowel disease and celiac disease: A Mendelian randomization study

Objective

To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.

Background

Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.

Methods

Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.

Results

Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction.

Conclusions

We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.     

Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.     

FTO, type 2 diabetes, and weight gain throughout adult life: a meta-analysis of 41,504 subjects from the Scandinavian HUNT, MDC, and MPP studies

OBJECTIVE

FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span.

RESEARCH DESIGN AND METHODS

Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians.

RESULTS

The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 × 10⁻⁸) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 × 10⁻⁸). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m² per risk allele; P = 2.0 × 10⁻²⁶), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (∆BMI = 0.0 [−0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults.

CONCLUSIONS

We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter.Genomewide association studies (GWAS) have identified a strong correlation between BMI and FTO single nucleotide polymorphisms (SNPs) (1–4), and the association has been confirmed in multiple populations (reviewed in 5). The FTO risk variants are also associated with obesity-related traits (6–8). However, these effects appear to be secondary to weight increase because the associations are attenuated after adjusting for BMI (2). In contrast, we and others have found that the association with type 2 diabetes may not be completely mediated through BMI, because it remains significant after BMI correction (9). This indicates that the relationship between sequence variation in FTO and type 2 diabetes is not fully mediated through BMI or that BMI in some populations does not reveal accurate estimates of the effect of FTO on adiposity.Various studies have investigated the effect of FTO variants on BMI and weight in a longitudinal perspective (10–18) but with diverging results. With access to extensive data from three large Scandinavian populations, through a meta-analysis approach using both cross-sectional and longitudinal data, we aimed to investigate whether the FTO risk allele affects type 2 diabetes risk after correction for BMI and whether it influences weight gain during adult life.     

Pollution Characteristics,Sources, and Health Risk Assessments of Potentially Toxic Elements in Community Garden Soil of Lin’an,Zhejiang, China

The characteristics, sources and risk assessment of heavy metal pollution in community garden soil of Lin’an District were evaluated. The 28 soil samples from community garden were collected for determination of 7 heavy metal elements. The Geostatistical analysis, Spearman correlation coefficient, Principal component analysis and PMF model have explored sources of heavy metal pollution. The health risk assessment model has assessed ecological risk of heavy metals. The results revealed that average concentration of As, Cd, Cr, Cu, Ni, Pb and Zn were 16.0, 0.158, 76.1, 34.6, 45.8, 20.9 and 166 mg kg^-1, respectively. Whereas As, Cd, Cr, Cu, Ni and Zn were higher than background values. The spatial distribution of heavy metal pollution in the southwest of the study area was higher than northeast. The pollution sources of Cd, Cu, Ni and Zn in the study area were due to agricultural activities (42.9%), Cr and Pb were from traffic sources (36.2%), and As was domestic pollution (20.9%) according to Spearman correlation coefficient, Principal component analysis and PMF model. The non-carcinogenic risks of As (5.39), Cr (3.53) and Ni (2.07) have a value of 1, which indicated significant risk. The potentially toxic elements have not exceeded maximum threshold of USEPA, with regard to carcinogenic risk, while As (3.37E?05) and Cr (5.74E?05) have exceeded the safety range. It is concluded that soils of community gardens are facing pollution problem due to potentially toxic elements which require environmental monitoring of the soil to reduce risk of human health.

     

Obstetrical correlates of the first time cesarean section, compared with the repeated cesarean section

Objective: To determine the clinical and epidemiological characteristics in patients having their first cesarean section (FCS) and compare it with findings in patients with repeated cesarean section (RCS). Design: A cross-sectional, comparative study. Place and Duration of Study: Unit 'A' of the Department of Obstetrics and Gynaecology, Postgraduate Medical Institute of Lady Reading Hospital, Peshawar, Pakistan, from January to December 2005. Patients and Methods: This study included all the women who gave birth by cesarean sections, 817 of the total 5992 deliveries, at this unit during the study period. Data on potential risk factors for the first cesarean section (FCS) and repeated cesarean section (RCS) were extracted from medical records, which were reviewed and compared between these two groups of women. Data were statistically analyzed with student t-test for comparison between means and Chi-square test for comparison between percentages. Crude odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Significance was taken at p < 0.05. Results: The incidence of cesarean sections was 13.62% of the total deliveries, with the FCS frequency of 70.13 % (573) and RCS frequency of 29.87% (244). The three most frequent indications for FCS were dystocia and cephalopelvic disproportion (42.8%), fetal distress (18.5%), and abnormal presentation (32.1%). Meanwhile, those for RCS were previous cesarean section (41%), dystocia (27.5%) and abnormal presentation (15.2%). The factors significantly associated with FCS were: age < 20 years, first pregnancy, premature rupture of membranes, antecedent of labor room induction and neonatal weight above 3500 g (p < 0.05). More cases of emergency cesarean sections, antipartum hemorrhage, malpresentations and traditional birth attendants (TBA's) handling were encountered in the FCS group (p < 0.05). Percentages of second gravidity and multigravidity were greater in RCS patients. Fetal outcome was also good in the RCS group. No difference between the groups was found regarding educational level and prenatal consultations (p > 0.05). Conclusion: The frequency of first cesarean section and repeat cesarean section is high in our setup. Adequate following of the programs to diminish the percentage of FCS by curtailing its predisposing factors is needed.