Challenging diagnoses of tetraploidy/diploidy and trisomy 12: utility of first-tier prenatal testing methods.

Introduction: Chromosome mosaicism and low-grade mosaicism present a challenge for diagnosis in the era of SNP array and NGS. Tetraploidy is a rare numerical chromosomal abnormality characterized by the presence of four copies of each chromosome. The prevalence of tetraploidy/diploidy mosaicism cases is extremely rare in the human population. Accurate estimates of the frequency of this chromosomal anomaly are lacking due to its classification as an extremely rare and difficult-to-detect condition. Methods: In this report, we describe two cases involving challenging diagnoses of tetraploidy/diploidy and trisomy 12. We utilized advanced genetic testing techniques, including SNP array, to examine the chromosomal abnormalities in these cases. We compared the results from SNP array to conventional G band karyotyping to assess the utility of first-tier prenatal testing methods. Results:Our analysis revealed two cases of tetraploidy/diploidy and trisomy 12 with atypical presentations. SNP array analysis provided higher resolution and more precise information about the chromosomal anomalies in these cases compared to conventional G band karyotyping. Additionally, the prevalence of tetraploidy/diploidy mosaicism was confirmed to be extremely rare in the population. Discussion: Low-level mosaicism is difficult to diagnose, and in many cases, it has traditionally been identified through techniques such as G band karyotype or FISH. Microarray has become an invaluable diagnostic tool for detecting chromosomal abnormalities, offering high-resolution insights. However, it may not always be able to detect rare occurrences of tetraploidy or tetraploidy/diploidy mosaicism. As a result, it is recommended to perform a G band karyotype analysis after obtaining a negative microarray result before considering other diagnostic methods with a potentially higher yield of diagnosis. For the detection of low-level mosaicism, combined diagnostic methods should be considered. The diagnosis of mosaicism is a multistep process that can be time-consuming, often requiring the application of more than one diagnostic technique. This approach is crucial for accurate diagnosis and comprehensive patient care. Further research is warranted to better understand the underlying mechanisms of these rare chromosomal anomalies and to develop more effective diagnostic strategies for challenging cases.

Maternal race and pre-eclampsia: Cohort study and systematic review with meta-analysis.

OBJECTIVES: To examine the association between race and pre-eclampsia and gestational hypertension after adjustment for factors in maternal characteristics and medical history in a screening study from the Fetal Medicine Foundation (FMF) in England, and to perform a systematic review and meta-analysis of studies on pre-eclampsia. DESIGN: Prospective observational study and systematic review with meta-analysis. SETTING: Two UK maternity hospitals. POPULATION: A total of 168 966 women with singleton pregnancies attending for routine ultrasound examination at 11-13 weeks of gestation without major abnormalities delivering at 24 weeks or more of gestation. METHODS: Regression analysis examined the association between race and pre-eclampsia or gestational hypertension in the FMF data. Literature search to December 2021 was carried out to identify peer-reviewed publications on race and pre-eclampsia. MAIN OUTCOME MEASURE: Relative risk of pre-eclampsia and gestational hypertension in women of black, South Asian and East Asian race by comparison to white women. RESULTS: In black women, the respective risks of total-pre-eclampsia and preterm-pre-eclampsia were 2-fold and 2.5-fold higher, respectively, and risk of gestational hypertension was 25% higher; in South Asian women there was a 1.5-fold higher risk of preterm pre-eclampsia but not of total-pre-eclampsia and in East Asian women there was no statistically significant difference in risk of hypertensive disorders. The literature search identified 19 studies that provided data on several million pregnancies, but 17 were at moderate or high-risk of bias and only three provided risks adjusted for some maternal characteristics; consequently, these studies did not provide accurate contributions on different racial groups to the prediction of pre-eclampsia. CONCLUSION: In women of black and South Asian origin the risk of pre-eclampsia, after adjustment for confounders, is higher than in white women.

Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp1.

A transient, homeostatic transcriptional response can result in transcriptional memory, programming subsequent transcriptional outputs. Transcriptional memory has great but unappreciated potential to alter animal aging as animals encounter a multitude of diverse stimuli throughout their lifespan. Here we show that activating an evolutionarily conserved, longevity-promoting transcription factor, dFOXO, solely in early adulthood of female fruit flies is sufficient to improve their subsequent health and survival in midlife and late life. This youth-restricted dFOXO activation causes persistent changes to chromatin landscape in the fat body and requires chromatin remodelers such as the SWI/SNF and ISWI complexes to program health and longevity. Chromatin remodeling is accompanied by a long-lasting transcriptional program that is distinct from that observed during acute dFOXO activation and includes induction of Xbp1. We show that this later-life induction of Xbp1 is sufficient to curtail later-life mortality. Our study demonstrates that transcriptional memory can profoundly alter how animals age.

Maternal inherited thrombophilia and pregnancy outcomes.

Thrombophilia is a group of genetical disorders that cause blood to clot abnormally. Thrombophilia is linked to recurrent pregnancy loss, foetal growth restriction, late miscarriages, stillbirth and preeclampsia. Clinicians usually apply the term thrombophilia only to patients with atypical thrombosis. A successful outcome of pregnancy requires an efficient uteroplacental circulation. Since this system may be compromised by disorders associated with a prothrombotic state, it was postulated that maternal thrombophilia might be a risk factor for preeclampsia and intrauterine growth retardation. The study included 459 pregnant women with gestational ages ranging from 14 weeks to 28 weeks and the patients in the study were tested for hereditary thrombophilia. The type of thrombophilic mutation most common found was the MTHFR mutation (25.7%), followed by the prothrombin gene mutation (20.9%) and the Leiden factor V mutation (15.7%). Also 15.03% patients had been diagnosed with preeclampsia and 6.75% of the pregnant women had IUGR fetuses.

Colon cancer in pregnancy: a diagnostic and therapeutic challenge.

Metastatic colorectal cancer during pregnancy and postpartum is rather rare, but it represents major diagnostic and therapeutic challenges for obstetricians and surgeons. Cancer itself rarely affects the placenta or growing baby directly. However, metastatic disease is much more common than in nonpregnant patients and detecting cancer while pregnant can be complicated for both the mother and the health care team. In this article, we report a case of moderately differentiated colon adenocarcinoma in pregnancy that was diagnosed in an advanced stage, implying a complex diagnostic and therapeutic approach. The classic histological and immunohistochemical (IHC) study on this case reveals that tumorous areas have lost goblet cells and, implicitly, mucus; also, there are absent estrogen and progesterone receptors, possible causes of neoplasm in pregnancy, the rate of tumor proliferation is increased, the IHC reaction that highlights the protein responsible for cytoplasmatic anchoring of cadherins is intense positive, and the enzyme responsible for inflammation and pain is increased in these areas.

Technical note: Applicability of tooth cementum annulation to an archaeological population.

The use of tooth cementum annulations for age determination has been deemed promising, exhibiting high correlations with chronological age. Despite its apparent potential, to date, the tooth cementum annulations method has been used rarely for estimating ages in archaeological populations. Here we examine the readability of cementum annulations and the consistency of age estimates using a sample of 116 adults from the Iron Gates Gorge Mesolithic/Neolithic series. Our examination of the method pointed to several sources of error that call into question the use of this method for estimating the chronological ages of archaeologically derived dental samples. The poor performance of the method in our analysis might be explained by taphonomic influences, including the effect of chemical and biological agents on dental microstructures.