Genetic Normalization of Differentiating Aneuploid Human Embryos

Early embryogenesis involves a series of dynamic processes, many of which are currently not well described or understood. Aneuploidy and aneuploid mosaicism, a mixture of aneuploid and euploid cells within one embryo, in early embryonic development are principal causes of developmental failure.^1,2^ Here we show that human embryos demonstrate a significant rate of genetic correction of aneuploidy, or "genetic normalization" when cultured from the cleavage stage on day 3 (Cleavage) to the blastocyst stage on day 5 (Blastocyst) using routine in vitro fertilization (IVF) laboratory conditions. One hundred and twenty-six human Cleavage stage embryos were evaluated for clinically indicated preimplantation genetic screening (PGS). Sixty-four of these embryos were found to be aneuploid following Cleavage stage embryo biopsy and single nucleotide polymorphism (SNP) 23 chromosome molecular karyotype (microarray). Of these, 25 survived to the Blastocyst stage of development and repeat microarray evaluation was performed. The inner cell mass (ICM), containing cells destined to form the fetus, and the trophectoderm (TE), containing cells destined to form the placenta were evaluated. Sixteen of 25 embryos (64%) [95% CI: 44-80%] possessed diploid karyotypes in both the ICM and TE cell populations. An additional three Blastocyst stage embryos showed genetic correction of the TE but not the ICM and one Blastocyst stage embryo showed the reverse. Mosaicism (exceeding 5%), was not detected in any of the ICM and TE samples analyzed. Recognizing that genetic normalization may occur in developing human embryos has important implications for stem cell biology, preimplantation and developmental genetics, embryology, and reproductive medicine. 

1)Hassold, T. et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 44, 151-78 (1980).
2)Menasha, J., Levy, B., Hirschhorn, K., & Kardon, N.B. Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med. 7, 251-63 (2005)

A Potential Alternative Orodispersible Formulation to Prednisolone Sodium Phosphate Orally Disintegrating Tablets

The orally disintegrating tablet (ODT) has shown vast potential as an alternative oral dosage form to conventional tablets wherein they can disintegrate rapidly (≤30 s) upon contact with saliva fluid and should have an acceptable mouthfeel as long as their weight doesn’t exceed 500 mg. However, owing to the bitterness of several active ingredients, there is a need to find a suitable alternative to ODTs that maintains their features and can be taste-masked more simply and inexpensively. Therefore, electrospun nanofibers and solvent-cast oral dispersible films (ODFs) are used in this study as potential OD formulations for prednisolone sodium phosphate (PSP) that is commercially available as ODTs. The encapsulation efficiency (EE%) of the ODFs was higher (≈100%) compared to the nanofibers (≈87%), while the disintegration time was considerably faster for the electrospun nanofibers (≈30 s) than the solvent-cast ODFs (≈700 s). Hence, accelerated release rate of PSP from the nanofibers was obtained, due to their higher surface area and characteristic surface morphology that permitted higher wettability and thus, faster erosion. Taste-assessment study using the electronic-tongue quantified the bitterness threshold of the drug and its aversiveness concentration (2.79 mM). Therefore, a taste-masking strategy would be useful when further formulating PSP as an OD formulation

Do Mismatches between Pre- and Post-Natal Environments Influence Adult Physiological Functioning?

Purpose: Mismatches between pre- and post-natal environments have implications for disease in adulthood. However, less is known about how this mismatch can affect physiological systems more generally, especially at younger ages. We hypothesised that mismatches between pre- and post-natal environments, as measured by the measures of birthweight and adult leg length, would be associated with poorer biomarker levels across five key physiological systems in young adults. Methods: Data were collected from 923, 36 year-old respondents from the West of Scotland Twenty-07 Study. The biomarkers were: systolic blood pressure (sBP); forced expiratory volume (FEV1); glycated haemoglobin (HbA1c); glomerular filtration rate (eGFR); and gamma- glutamyltransferase (GGT). These biomarkers were regressed against pre-natal conditions (birthweight), post-natal conditions (leg length) and the interaction between pre- and post-natal measures. Sex, childhood socioeconomic position and adult lifestyle characteristics were adjusted for as potential effect modifiers and confounders, respectively. Results: There were no associations between birthweight and leg length and sBP, FEV1, HbA1c, or GGT. Higher birthweight and longer leg length were associated with better kidney function (eGFR). However, there was no evidence for mismatches between birthweight and leg length to be associated with worse sBP, FEV1, HbA1c, eGFR or GGT levels (P>0.05). Conclusions: Our hypothesis that early signs of physiological damage would be present in young adults given mismatches in childhood environments, as measured by growth markers, was not proven. This lack of association could be because age 36 is too young to identify significant trends for future health, or the associations simply not being present. © 2014 Robertson, Benzeval

Pregnancy-induced hypertension and infant growth at 28 and 42 days postpartum

BACKGROUND: No previous studies have examined the effect of pregnancy-induced hypertension (PIH) on early infant growth. The objective was to study infant growth patterns of babies born to mothers with PIH at 28 and 42 days postpartum. METHODS: DESIGN: We conducted a population-based retrospective cohort study of 16,936 pregnancies delivered between January 1, 1989 through December 31, 1990 in Suzhou, China. PIH was classified as gestational hypertension, preeclampsia and severe preeclampsia. Infant Growth Percentage (IGP) was calculated as the weight gain from birth to infant weight at 28 or 42 days postpartum divided by the birth weight. Univariate analysis and multivariate linear regression were performed to compare the infant weight as well as IGP at 28 and 42 days postpartum between various types of PIH and the normotensive group. RESULTS: Infant weights at 28 and 42 days postpartum were significantly lower in severe preeclampsia (e.g., 4679.9 g at 42 days) and preeclampsia (e.g., 4763.8 g at 42 days) groups than in the normotensive group (e.g., 4869.1 g at 42 days, p < 0.01). However, there were no differences in IGP between groups. After stratifying by intrauterine growth restriction (IUGR) status, if babies were not intrauterine growth restricted, none of the PIH types showed a significantly lower weight at 28 and 42 days postpartum and their IGPs were similar to those of the reference group. When babies were growth restricted, all PIH groups showed significantly lower weights but higher IGP at 28 and 42 days postpartum as compared to the normotensive group. CONCLUSION: Infants born to mothers with PIH but without IUGR have normal early infant growth. IUGR secondary to PIH is associated with significant catch-up growth at 28 and 42 days postpartum

Lemierre Syndrome: A Case of Postanginal Sepsis

Lemierre syndrome is a rare disease that's characterized by internal jugular vein thrombosis and septic emboli. These symptoms typically develop after acute oropharyngeal infection by Fusobacterium necrophorum1). Although this syndrome is less frequently seen in modern times due to the availability of antibiotics, physicians must be aware of the syndrome in order to initiate prompt antibiotics therapy, including coverage of the anerobic organisms. We discuss here the case of an 18-year-old female with Lemierre syndrome and we review the relevant literature on this syndrome

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center, Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002

International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO)

Reviews find a likely adverse effect of air pollution on perinatal outcomes, but variation of findings hinders the ability to incorporate the research into policy. The International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) was formed to better understand relationships between air pollution and adverse birth outcomes through standardized parallel analyses in datasets from different countries. A planning group with 10 members from 6 countries was formed to coordinate the project. Collaboration participants have datasets with air pollution values and birth outcomes. Eighteen research groups with data for approximately 20 locations in Asia, Australia, Europe, North America, and South America are participating, with most participating in an initial pilot study. Datasets generally cover the 1990s. Number of births is generally in the hundreds of thousands, but ranges from around 1,000 to about one million. Almost all participants have some measure of particulate matter, and most have ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide. Strong enthusiasm for participating and a geographically-diverse range of participants should lead to understanding uncertainties about the role of air pollution in perinatal outcomes and provide decision-makers with better tools to account for pregnancy outcomes in air pollution policies

Relationship between birth weight and retinal microvasculature in newborn infants

Objective: The purposes of this study were to determine the normal retinal microvasculature measurements in human infants who are born at term and to determine whether birth weight influences measurements of retinal microvasculature. Study Design: Retinal arteriole and venule measurements were obtained in a cohort of 24 infants who were born at term. Digital images of both the retinas were obtained using a digital retinal camera after pupillary dilation. Result: In all, 24 newborn infants born at term (12 females and 12 males) were analyzed in this study. The measured retinal arteriole diameters were from 66.8 to 147.8 μm (mean, 94.2±19.6 μm), and the venule diameters were from 102.0 to 167.8 μm (mean, 135.2±19.1 μm). Seven babies in the sample had low birth weight (LBW), while 17 babies were born with normal weight. Babies with lower birth weights had larger arteriole (113.1±17.9 μm vs 86.4±14.4 μm; P=0.0009) and venule diameters (151.7±14.9 μm vs 128.4±16.9 μm; P=0.0040). Conclusion: Retinal venules and arterioles in LBW babies are larger compared with those of normal-birth-weight babies. We postulate that the difference observed in our study was due to in utero pathophysiological changes that occurred in the cerebral circulation of growth-restricted fetuses