Current knowledge about human development is based on the description of a limited number of embryonic specimens published in original articles and textbooks, often more than 100 years ago. It is exceedingly difficult to verify this knowledge, given the restricted availability of human embryos. We created a three-dimensional digital atlas and database spanning the first 2 months of human development, based on analysis of nearly 15,000 histological sections of the renowned Carnegie Collection of human embryonic specimens. We identified and labeled up to 150 organs and structures per specimen and made three-dimensional models to quantify growth, establish changes in the position of organs, and clarify current ambiguities. The atlas provides an educational and reference resource for studies on early human development, growth, and congenital malformations.

ObjectiveType 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).DesignPatients with recent-onset (<6 weeks) T1D (18–30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.ResultsStimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=−0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.ConclusionFMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.Trial registration numberNTR3697.

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Background MRI and CT have been extensively used to study fetal anatomy for research and diagnostic purposes, enabling minimally invasive autopsy and giving insight in human fetal development. Novel (contrast-enhanced) microfocus CT (micro-CT) and ultra-high-field (≥ 7.0 T) MRI (UHF-MRI) techniques now enable micron-level resolution that combats the disadvantages of low-field MRI and conventional CT. Thereby, they might be suitable to study fetal anatomy in high detail and, in time, contribute to the postmortem diagnosis of fetal conditions. Objectives (1) To systematically examine the usability of micro-CT and UHF-MRI to study postmortem human fetal anatomy, and (2) to analyze factors that govern success at each step of the specimen preparation and imaging. Method MEDLINE and EMBASE were systematically searched to identify publications on fetal imaging by micro-CT or UHF-MRI. Scanning protocols were summarized and best practices concerning specimen preparation and imaging were enumerated. Results Thirty-two publications reporting on micro-CT and UHF-MRI were included. The majority of the publications focused on imaging organs separately and seven publications focused on whole body imaging, demonstrating the possibility of visualization of small anatomical structures with a resolution well below 100 μm. When imaging soft tissues by micro-CT, the fetus should be stained by immersion in Lugol's staining solution.Conclusion Micro-CT and UHF-MRI are both excellent imaging techniques to provide detailed images of gross anatomy of human fetuses. The present study offers an overview of the current best practices when using micro-CT and/or UHF-MRI to study fetal anatomy for clinical and research purposes. Key Points • Micro-CT and UHF-MRI can both be used to study postmortem human fetal anatomy for clinical and research purposes.• Micro-CT enables high-resolution imaging of fetal specimens in relatively short scanning time. However, tissue staining using a contrast solution is necessary to enable soft-tissue visualization. • UHF-MRI enables high-resolution imaging of fetal specimens, without the necessity of prior staining, but with the drawback of long scanning time.

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Diffusible iodine-based contrast-enhanced computed tomography (diceCT) is progressively used in clinical and morphological research to study developmental anatomy. Lugol’s solution (Lugol) has gained interest as an effective contrast agent; however, usage is limited due to extensive soft-tissue shrinkage. The mechanism of Lugol-induced shrinkage and how to prevent it is largely unknown, hampering applications of Lugol in clinical or forensic cases where tissue shrinkage can lead to erroneous diagnostic conclusions. Shrinkage was suggested to be due to an osmotic imbalance between tissue and solution. Pilot experiments pointed to acidification of Lugol, but the relation of acidification and tissue shrinkage was not evaluated. In this study, we analyzed the relation between tissue shrinkage, osmolarity and acidification of the solution during staining. Changes in tissue volume were measured on 2D-segmented magnetic resonance and diceCT images using AMIRA software. Partial correlation and stepwise regression analysis showed that acidification of Lugol is the main cause of tissue shrinkage. To prevent acidification, we developed a buffered Lugol’s solution (B-Lugol) and showed that stabilizing its pH almost completely prevented shrinkage without affecting staining. Changing from Lugol to B-Lugol is a major improvement for clinical and morphological research and only requires a minor adaptation of the staining protocol.

Evolutionary responses to selection for bipedalism and childbirth have shaped the human pelvis, a structure that differs substantially from that in apes. Morphology related to these factors is present by birth, yet the developmental-genetic mechanisms governing pelvic shape remain largely unknown. Here, we pinpoint and characterize a key gestational window when human-specific pelvic morphology becomes recognizable, as the ilium and the entire pelvis acquire traits essential for human walking and birth. We next use functional genomics to molecularly characterize chondrocytes from different pelvic subelements during this window to reveal their developmental-genetic architectures. We then find notable evidence of ancient selection and genetic constraint on regulatory sequences involved in ilium expansion and growth, findings complemented by our phenotypic analyses showing that variation in iliac traits is reduced in humans compared to African apes. Our datasets provide important resources for musculoskeletal biology and begin to elucidate developmental mechanisms that shape human-specific morphology.

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