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We present a case of a fetus acquiring two different balanced translocations from each parent and subsequent uniparental isodisomy from postzygotic loss of a paternal chromosome. Balanced chromosomal translocations occur in 0.14% of the population and increase the risk of other genetic abnormalities, such as uniparental disomy (UPD) and mosaicism. Preimplantation genetic testing (PGT) can identify some genetic abnormalities. Translocations t(6;21) and t(5;15) have been reported individually but never together in a viable fetus. A non-consanguineous couple who were known carriers of two different balanced translocations conceived via classic in vitro fertilization (IVF). They had a normal PGT completed. Chorionic villus sampling (CVS) revealed that the fetus had received t(6;21) from the mother and t(5;15) from the father. The probability of the fetus acquiring both translocations was 2.8%. CVS also revealed UPD of chromosome 14. Amniocentesis was performed, which was consistent with the CVS in detecting the balanced translocations but provided more information about the UPD, determining that it was a mosaic maternal uniparental isodisomy of chromosome 14 (UPD(14)mat). The couple underwent genetic counseling to discuss the above findings and ultimately decided on dilation and evacuation at 17 weeks of gestation. The likelihood of conception of this fetus and survival past the first trimester is extremely rare. These specific chromosomal translocations and (UPD(14)mat) have never been reported before. This case emphasizes the concomitant nature of imprinted genes, resulting in multiple genetically unique alterations. This report also highlights the limitations of PGT, CVS, and amniocentesis in being reproducibly consistent, which is important to discuss prior to IVF conception.
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The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.
Asunto(s)
Heterocromatina , Oocitos , Animales , Heterocromatina/genética , Heterocromatina/metabolismo , Cromatina/genética , Cromatina/metabolismo , Histonas/metabolismo , Ensamble y Desensamble de Cromatina , Mamíferos/genéticaRESUMEN
Introduction The Affordable Care Act has been debated since its initial enactment over a decade ago. One of the primary topics for discussion has been Medicaid expansion, which has created a schism across the United States. The effects of Medicaid expansion largely remain unclear. The purpose of this report is to elucidate how Medicaid expansion has impacted emergency department (ED) utilization by analyzing Medicaid expansion and non-expansion states to determine who visited the ED and the reason for the visit. Methods We conducted a retrospective analysis using de-identified electronic medical record (EMR) data from 56,423 patients and 33 different hospitals (18 Medicaid non-expansion and 15 Medicaid expansion) who visited the ED in 2019. We used geographical demographics and insurance status to categorize patients who visited the ED and ambulatory care sensitive conditions (ACSC) to identify the reasons for the visit. Logistic regression and chi-square analysis were used to analyze the data. Results We observed a significant relationship between Medicaid expansion and geographic region such that patients living in rural or semirural regions likely resided in Medicaid non-expansion states. Patients using self-pay were more likely to live in a Medicaid non-expansion state than a Medicaid expansion state (32.3% vs. 21.5%, p-value < 0.0001). Finally, there were no significant differences between the top five ACSC for Medicaid expansion and Medicaid non-expansion states but living in an expansion state was significantly (p < 0.01) related to being diagnosed with an ACSC (OR, 1.056; 95% CI, 1.013-1.100). Conclusion In conclusion, Medicaid expansion was associated with differences in the use of medical resources. Patients using Medicaid insurance who reside in Medicaid expansion states preferentially use the ED. Geographical location does play a role in ED utilization and ambulatory care sensitive condition diagnoses in patients. Despite these findings, the full effects of Medicaid expansion on ED utilization require further investigation. However, our research indicates that Medicaid expansion is not the singular solution in decreasing ED utilization and healthcare costs.
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Hepatic cirrhosis, diabetes mellitus and iron overload can each independently predispose to cryptococcosis. Hereditary hemochromatosis leads to all three of these predispositions. This report is the case of a patient with chronic hepatitis B virus infection and cirrhosis, who had markedly elevated serum ferritin and 99% transferrin saturation, and developed a leukemoid reaction. Autopsy revealed disseminated cryptococcosis for which the leukemoid reaction was a clue and possible hereditary hemochromatosis of which elevated ferritin and transferrin saturation can be clues. Hereditary hemochromatosis is an important diagnosis clinicians should never miss because early treatment with phlebotomy can be life-saving. Disseminated cryptococcosis can be rapidly diagnosed with serum cryptococcal antigen test and is treatable.
RESUMEN
Hepatic cirrhosis, diabetes mellitus and iron overload can each independently predispose to cryptococcosis. Hereditary hemochromatosis leads to all three of these predispositions. This report is the case of a patient with chronic hepatitis B virus infection and cirrhosis, who had markedly elevated serum ferritin and 99% transferrin saturation, and developed a leukemoid reaction. Autopsy revealed disseminated cryptococcosis for which the leukemoid reaction was a clue and possible hereditary hemochromatosis of which elevated ferritin and transferrin saturation can be clues. Hereditary hemochromatosis is an important diagnosis clinicians should never miss because early treatment with phlebotomy can be life-saving. Disseminated cryptococcosis can be rapidly diagnosed with serum cryptococcal antigen test and is treatable.