An Infancy-Onset 20-Year Dietary Counselling Intervention and Gut Microbiota Composition in Adulthood

The randomized controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) has completed a 20-year infancy-onset dietary counselling intervention to reduce exposure to atherosclerotic cardiovascular disease risk factors via promotion of a heart-healthy diet. The counselling on, e.g., low intake of saturated fat and cholesterol and promotion of fruit, vegetable, and whole-grain consumption has affected the dietary characteristics of the intervention participants. By leveraging this unique cohort, we further investigated whether this long-term dietary intervention affected the gut microbiota bacterial profile six years after the intervention ceased. Our sub-study comprised 357 individuals aged 26 years (intervention n = 174, control n = 183), whose gut microbiota were profiled using 16S rRNA amplicon sequencing. We observed no differences in microbiota profiles between the intervention and control groups. However, out of the 77 detected microbial genera, the Veillonella genus was more abundant in the intervention group compared to the controls (log₂ fold-change 1.58, p < 0.001) after adjusting for multiple comparison. In addition, an association between the study group and overall gut microbiota profile was found only in males. The subtle differences in gut microbiota abundances observed in this unique intervention setting suggest that long-term dietary counselling reflecting dietary guidelines may be associated with alterations in gut microbiota.     

Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and Skin in Breast MRI

Mammographic breast density (MBD) is the most commonly used method to assess the volume of fibroglandular tissue (FGT). However, MRI could provide a clinically feasible and more accurate alternative. There were three aims in this study: (1) to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess the inter-rater agreement of MRI-based volumetric measurements and (3) to compare them to measurements acquired using digital mammography and 3D tomosynthesis. This retrospective study examined 72 women (mean age 52.4 ± 12.3 years) with 105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either digital mammography or tomosynthesis. Two observers analyzed MRI images for breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm-thick slices) using K-means clustering, data from histogram, and active contour algorithms. Reference values were obtained with Quantra software. Inter-rater agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT-%, r = 0.994 (95% CI 0.990–0.997); for breast volume, r = 0.985 (95% CI 0.934–0.994); and for FGT volume, r = 0.979 (95% CI 0.958–0.989). MRI-based FGT-% correlated strongly with MBD in mammography (r = 0.819–0.904, P < 0.001) and moderately to high with MBD in tomosynthesis (r = 0.630–0.738, P < 0.001). K-means clustering-based assessments of the proportion of the fibroglandular tissue in the breast at MRI are highly reproducible. In the future, quantitative assessment of FGT-% to complement visual estimation of FGT should be performed on a more regular basis as it provides a component which can be incorporated into the individual’s breast cancer risk stratification.     

Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity

Objectives: Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype.

Materials and methods: We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses.

Results: No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n?=?9) and the control children without disease or associated autoantibodies (n?=?18).

Conclusions: Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.     

Is bone loss the reversal of bone accrual? evidence from a cross‐sectional study in daughter‐mother‐grandmother trios

Bone adapts to mechanical loads applied on it. During aging, loads decrease to a greater extent at those skeletal sites where loads increase most in earlier life. Thus, the loss of bone may occur preferentially at sites where most bone has been deposited previously; ie, bone loss could be the directional reversal of accrual. To test this hypothesis, we compared the bone mass distribution at weight‐bearing (tibia) and non‐weight‐bearing (radius) bones among 18‐year‐old girls, their premenopausal mothers, and their postmenopausal maternal grandmothers. Bone and muscle properties were measured by pQCT, and polar distribution of bone mass was obtained in 55 girl‐mother–maternal grandmother trios. Site‐matched differences in bone mass were compared among three generations. The differences between girls and mothers and between mothers and grandmothers were used to represent the patterns of bone mass accrual from early adulthood to middle age and bone loss from middle to old age, respectively. Compared to the mothers, 18‐year old girls had less bone mass in the anterior and medial‐posterior regions of the tibial shaft, while the grandmothers had less bone in the anterior and posterior regions. In contrast, the bone mass differences in the radial shaft between girls and mothers and mothers and grandmothers were relatively uniform. We conclude that both bone accrual and loss are direction‐specific in weight‐bearing bones but relatively uniform in non‐weight‐bearing bones. Bone loss in old age is largely, but not completely, a reversal of the preferential deposition of bone in the most highly loaded regions during early life. © 2011 American Society for Bone and Mineral Research.     

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans.

We investigated the biodistribution and radiation dosimetry of the PET amyloid imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in humans. Previous radiation exposure estimates have been based on animal experiments. A dosimetry study in humans is essential for a balanced risk-benefit assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of these scans were dynamic imaging over the abdominal region: 3 covering the upper abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were recorded for up to 40 min. Two subjects had whole-body imaging over the entire body to illustrate the biodistribution. PET brain scans and blood and urine radioactivity measurements from our previous (11)C-PIB studies were also analyzed. Thirteen source organs and the remainder of the body were studied to estimate residence times and mean radiation-absorbed doses. The MIRD method was used to calculate the radiation exposure of selected target organs and the body as a whole. RESULTS: There is a high degree of consistency between our human data and previous biodistribution information based on baboons. In our study, the highest radiation-absorbed doses were received by the gallbladder wall (41.5 microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq), kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The hepatobiliary and renal systems were the major routes of clearance and excretion, with approximately 20% of the injected radioactivity being excreted into urine. The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is comparable with the average exposure expected in other PET brain receptor tracer studies. (11)C-PIB is rapidly cleared from the body, largely by the kidneys. From the viewpoint of radiation safety, these results support the use of (11)C-PIB in clinical PET studies.     

Reliability of cranial base measurements on lateral skull radiographs

Authors – Arponen H, Elf H, Evälahti M, Waltimo‐Sirén J Objective – To explore the reliability of identification of anatomic landmarks on lateral skull radiographs of young unaffected individuals that has conventionally been used to diagnose pathologic relationships in the craniovertebral junction. Material and Methods – From the Helsinki longitudinal growth study, 20 randomly selected lateral radiographs were analyzed and re‐analyzed by two examiners. Both located seven cephalometric landmarks based on which five measurements were calculated. The differences of results were compared. With similar method three radiographs were analysed by 11 examiners and results were compared. Results – Some anatomic landmarks were easier to locate than others on lateral skull radiographs leading to differences in measurements based on them. We found the magnitude of the difference to be dependent on the landmark serving as reference. Inter‐ and intra‐examiner errors were of similar magnitude, although intra‐examiner error declined in the repeated landmark identification. Variation in a single landmark location had in general little effect on the measurement value. Conclusion – Variations in landmark location lead to differences in numeric evaluation of the anatomic relationships in the skull base area. These differences were, however, shown to have little clinical significance. Hence, the documented methods are applicable for screening of basilar pathology.