A Maternal High-Fat, High-Sucrose Diet Has Sex-Specific Effects on Fetal Glucocorticoids with Little Consequence for Offspring Metabolism and Voluntary Locomotor Activity in Mice

Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, in samples of 13,633 to 33,959 participants aged 5-26 years. We identified genome-wide significant association with word reading (rs11208009, p=1.098 x 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP-heritability, accounting for 13-26% of trait variability. Genomic structural equation modelling revealed a shared genetic factor explaining most variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain, and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of uniquely human traits

Validation of Panoramic Ultrasound Measurement of the Cross-Sectional Area of the Vastus Medialis

Minnehan, KS, Dexter, WW, Holt, CT, Scharnetzki, L, Alex, JP, Chin, KE, and Kokmeyer, DJ. Validation of panoramic ultrasound measurement of the cross-sectional area of the vastus medialis. J Strength Cond Res 37(1): 41-45, 2023-The cross-sectional area (CSA) of the vastus medialis (VM) is an independent predictor of important clinical outcomes in musculoskeletal conditions of the knee, such as pain and long-term function. Previous studies validated ultrasound (US) to measure larger muscles of the thigh, but this approach has limited accuracy in measuring smaller muscles, such as the VM. In this study, we aimed to validate panoramic US measurements of the CSA of the VM and compare the results with those from the gold standard of magnetic resonance imaging (MRI) (significance set p ≤ 0.05). In this retrospective, single-center study, we compared pairs of US and MRIs taken of 25 adults who participated in a 10-week study of non-weight-bearing activity at a National Aeronautics and Space Administration facility. Images were acquired from various locations on the right thigh at multiple time points. Two researchers independently analyzed the US and MRI pairs by outlining the intermuscular border of the VM in the most distal image. We found excellent agreement between the US and MRI measurements of the CSA of the VM analyzed by researcher 1 (interclass correlation coefficient [ICC]: 0.997) and researcher 2 (ICC: 0.980). We also found excellent agreement for interrater reliability for MRI (ICC: 0.988) and US (ICC: 0.982) and intrarater reliability for US for researcher 1 (ICC: 0.999) and researcher 2 (ICC: 0.996). Our findings demonstrate that US is a valid and reliable tool for measuring the CSA of the VM compared with MRI

Cellular versus acellular matrix devices in the treatment of diabetic foot ulcers: Interim results of a comparative efficacy randomized controlled trial

Healing of diabetic foot ulcers is a major challenge. Despite adhering to optimal standard of care (SOC), less than 30% of wounds heal after 20 weeks. Advanced cellular tissue‐based products have shown better healing over SOC, albeit with great cost and modest improvement. We hypothesized no difference in healing effected by either cellular (Dermagraft), noncellular (Oasis) devices, relative to SOC in treating diabetic foot ulcer in a randomized controlled trial. The primary and secondary outcomes were the percentage of subjects that achieved complete wound closure by study endpoint (12 weeks of treatment) and study completion, respectively. During the 2‐week screening phase with SOC, subjects with 40% change in ulcer size were excluded. After randomization, 56 patients entered an active treatment phase (8 weeks) followed by a maintenance phase (4‐week SOC), with endpoint at visit 15, and 4 monthly follow‐up visits. There was equal distribution of demographic data (p>.05) and no difference in initial wound characteristics (p>.05) between all groups. No differences were observed in complete wound closure by 12 and 28 weeks of treatment, nor were there any difference in percentage area reduction from treatment weeks 1 to 12 and from treatment weeks 1 to 28 between the groups. Each of the treatment arms showed statistically significant reduction in wound area from treatment weeks 1 to 28 (p<.05). This exploratory analysis suggests that the outcomes of treatment with either Dermagraft or Oasis matrix are comparable. We have completed enrollment, and the final data analysis is underway to make definitive conclusions