Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes.

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.

Analysis of Emergency Department Utilization in Medicaid Expansion and Non-expansion States.

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.

Disseminated cryptococcosis and hemochromatosis: clues to diagnosis.

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.

Disseminated cryptococcosis and hemochromatosis: clues to diagnosis

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.