Project description:BackgroundGreater epidemiologic understanding of the relationships among fetal-infant mortality and its prognostic factors, including birthweight, could have vast public health implications. A key step toward that understanding is a realistic and tractable framework for analyzing birthweight distributions and fetal-infant mortality. The present paper is the second of a two-part series that introduces such a framework.MethodsWe propose estimating birthweight-specific mortality within each component of a normal mixture model representing a birthweight distribution, the number of components having been determined from the data rather than fixed a priori.ResultsWe address a number of methodological issues related to our proposal, including the construction of confidence intervals for mortality risk at any given birthweight within a component, for odds ratios comparing mortality within two different components from the same population, and for odds ratios comparing mortality within analogous components from two different populations. As an illustration we find that, for a population of white singleton infants, the odds of mortality at 3000 g are an estimated 4.15 times as large in component 2 of a 4-component normal mixture model as in component 4 (95% confidence interval, 2.04 to 8.43). We also outline an extension of our framework through which covariates could be probabilistically related to mixture components. This extension might allow the assertion of approximate correspondences between mixture components and identifiable subpopulations.ConclusionsThe framework developed in this paper does not require infants from compromised pregnancies to share a common birthweight-specific mortality curve, much less assume the existence of an interval of birthweights over which all infants have the same curve. Hence, the present framework can reveal heterogeneity in mortality that is undetectable via a contaminated normal model or a 2-component normal mixture model.
Project description:The effective performance of fetal cardiac examination using spatiotemporal image correlation (STIC) technology requires 2 essential steps: volume acquisition and postprocessing. An important prerequisite is training sonologists to acquire high-quality volume data sets so that when analyzed, such volumes are informative. This article is part 2 of a series on 4-dimensional sonography with STIC. Part 1 focused on STIC technology and its features, the importance of operator training/experience and acquisition of high-quality STIC volumes, factors that affect STIC volume acquisition rates, and general recommendations on performing 4D sonography with STIC. In part 2, we discuss a detailed and practical stepwise approach for STIC volume acquisition, along with methods to determine whether such volumes are appropriate for analysis.
Project description:Four-dimensional sonography with spatiotemporal image correlation (STIC) technology allows acquisition of a fetal cardiac volume data set and displays a cine loop of a complete single cardiac cycle in motion. Part 1 of this 2-part article reviews STIC technology and its features, the importance of operator training/experience, and acquisition of high-quality STIC volumes, as well as factors that affect STIC volume acquisition rates. We also propose a detailed and practical stepwise approach to performing 4-dimensional sonography with STIC and begin herein by providing general recommendations. Part 2 will discuss specifics of the approach, along with how to determine whether such volumes are appropriate for analysis.
Project description:IntroductionThe immune compartment within fetal chorionic villi is comprised of fetal Hofbauer cells (HBC) and invading placenta-associated maternal monocytes and macrophages (PAMM). Recent studies have characterized the transcriptional profile of the first trimester (T1) placenta; however, the phenotypic and functional diversity of chorionic villous immune cells at term (T3) remain poorly understood.MethodsTo address this knowledge gap, immune cells from human chorionic villous tissues obtained from full-term, uncomplicated pregnancies were deeply phenotyped using a combination of flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) and chromatin accessibility profiling (snATAC-seq).ResultsOur results indicate that, relative to the first trimester, the frequency of fetal macrophages (HBC, proliferating HBC) is significantly reduced, whereas that of infiltrating maternal monocytes/macrophages (PAMM1b, PAMM1a, PAMM2, MAC_1) increased in T3. PAMM1b and HBCs exhibit the most phagocytic capacity at term highlighting their regulatory role in tissue homeostasis in late pregnancy. The transcriptional profiles of resident villous immune subsets exhibit a heightened activation state relative to the relative to T1, likely to support labor and parturition. Additionally, we provide one of the first insights into the chromatin accessibility profile of villous myeloid cells at term. We next stratified our findings by pre-pregnancy BMI since maternal pregravid obesity is associated with several adverse pregnancy outcomes. Pregravid obesity increased inflammatory gene expression, particularly among HBC and PAMM1a subsets, but dampened the expression of antimicrobial genes, supporting a tolerant-like phenotype of chorionic villous myeloid cells. We report a decline in HBC abundance accompanied by an increase in infiltrating maternal macrophages, which aligns with reports of heightened chorionic villous inflammatory pathologies with pregravid obesity. Finally, given the shared fetal yolk-sac origin of HBCs and microglia, we leveraged an in vitro model of umbilical cord blood-derived microglia to investigate the impact of pregravid obesity on fetal neurodevelopment. Our findings reveal increased expression of activation markers albeit dampened phagocytic capacity in microglia with pregravid obesity.DiscussionOverall, our study highlights immune adaptations in the fetal chorionic villous with gestational age and pregravid obesity, as well as insight towards microglia dysfunction possibly underlying poor neurodevelopmental outcomes in offspring of women with pregravid obesity.
Project description:In biological systems lipids generate membranes and have a key role in cell signaling and energy storage. Therefore, there is a wide diversity of molecular lipid expressed at the compositional level in cell membranes and organelles, as well as in tissues, whose lipid distribution remains unclear. Here, we report a mass spectrometry study of lipid abundance across 7 rat tissues, detecting and quantifying 652 lipid molecular species from the glycerolipid, glycerophospholipid, fatty acyl, sphingolipid, sterol lipid and prenol lipid categories. Our results demonstrate that every tissue analyzed presents a specific lipid distribution and concentration. Thus, glycerophospholipids are the most abundant tissue lipid, they share a similar tissue distribution but differ in particular lipid species between tissues. Sphingolipids are more concentrated in the renal cortex and sterol lipids can be found mainly in both liver and kidney. Both types of white adipose tissue, visceral and subcutaneous, are rich in glycerolipids but differing the amount. Acylcarnitines are mainly in the skeletal muscle, gluteus and soleus, while heart presents higher levels of ubiquinone than other tissues. The present study demonstrates the existence of a rat tissue-specific fingerprint.
Project description:BackgroundHypertrophic cardiomyopathy (HCM) in newborns is a rare condition with heterogeneous etiologies. While the relationship between hyperinsulinism and cardiac hypertrophy (CH) is known, hyperinsulinism has not been reported as cause of HCM.Case presentationWe report the case of cardiac hypertrophy (CH) in an Extremely Low Birth Weight (ELBW) infant; this patient underwent insulin therapy after the onset of persistent hyperglycemia due to parenteral nutrition (PN), supporting the hypothesis of a role of iatrogenic hyperinsulinemia in the development of HCM.ConclusionsThe present case underlines the importance of a close cardiological follow-up in infants undergoing insulin infusion for an alteration in the glucose metabolism.
Project description:BackgroundThe evidence on prematurity as 'a priori' a risk for palatal disturbances that increase the need for orthodontic or orthognathic treatment is still weak. Further well-designed clinical studies are needed. The objective of this review is to provide a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development. One focus of this review is the analysis of studies on the palate of the term newborn, since knowing what is 'normal' is a precondition of being able to assess abnormalities.MethodsA search profile based on Cochrane search strategies applied to 10 medical databases was used to identify existing studies. Articles, mainly those published before 1960, were identified from hand searches in textbooks, encyclopedias, reference lists and bibliographies. Sources in English, German, and French of more than a century were included. Data for term infants were recalculated if particular information about weight, length, or maturity was given. The extracted values, especially those from non-English paper sources, were provided unfiltered for comparison.ResultsThe search strategy yielded 182 articles, of which 155 articles remained for final analysis. Morphology of the term newborn's palate was of great interest in the first half of the last century. Two general methodologies were used to assess palatal morphology: visual and metrical descriptions. Most of the studies on term infants suffer from lack of reliability tests. The groove system was recognized as the distinctive feature of the infant palate. The shape of the palate of the term infant may vary considerably, both visually and metrically. Gender, race, mode of delivery, and nasal deformities were identified as causes contributing to altered palatal morphology. Until today, anatomical features of the newborn's palate are subject to a non-uniform nomenclature.ConclusionToday's knowledge of a newborn's 'normal' palatal morphology is based on non-standardized and limited methodologies for measuring a three-dimensional shape. This shortcoming increases bias and is the reason for contradictory research results, especially if pathologic conditions like syndromes or prematurity are involved. Adequate measurement techniques are needed and the 'normal palatal morphology' should be defined prior to new clinical studies on palatal development.
Project description:BackgroundHemodynamic and functional evaluation with Doppler and tissue Doppler study as a part of comprehensive echocardiography is essential but normal reference values have never been reported from Korean normal population especially according to age and sex.MethodsUsing Normal echOcaRdiographic Measurements in a KoreAn popuLation study subjects, we obtained normal reference values for Doppler and tissue Doppler echocardiography including tricuspid annular velocities according to current guidelines and compared values according to gender and age groups.ResultsMitral early diastolic (E) and late diastolic (A) velocity as well as E/A ratio were significantly higher in women compared to those in men. Conversely, mitral peak systolic and late diastolic annular velocity in both septal and lateral mitral annulus were significantly lower in women compared to those in men. However, there were no significant differences in both septal and lateral mitral early diastolic annular (e') velocity between men and women. In both men and women, mitral E velocity and its deceleration time as well as both E/A and E/e' ratio considerably increased with age. There were no significant differences in tricuspid inflow velocities and tricuspid lateral annular velocities between men and women except e' velocity, which was significantly higher in women compared to that in men. However, changes in both tricuspid inflow and lateral annular velocities according to age were similar to those in mitral velocities.ConclusionSince there were significant differences in Doppler and tissue Doppler echocardiographic variables between men and women and changes according to age were even more considerable in both gender groups, normal Doppler echocardiographic values should be differentially applied based on age and sex.