BACKGROUND: Risk factors for severe acute respiratory syndrome coronavirus 2 infection in pregnancy remain poorly understood. Identifying and understanding populations at a heightened risk of acquisition is essential to more effectively target outreach and prevention efforts. OBJECTIVE: This study aimed to compare sociodemographic and clinical characteristics of pregnant women with and without severe acute respiratory syndrome coronavirus 2 infection and, among those with severe acute respiratory syndrome coronavirus 2, to compare characteristics of those who reported coronavirus disease symptoms and those who were asymptomatic at diagnosis. STUDY DESIGN: This retrospective cohort study includes pregnant women who delivered or intended to deliver at Northwestern Memorial Hospital after initiation of a universal testing protocol on admission (April 8, 2020eMay 31, 2020). Women were dichotomized by whether they had a positive test result for severe acute respiratory syndrome coronavirus 2. Among women with a positive test result, women were further dichotomized by whether they reported symptoms of coronavirus disease 2019. Bivariable analysis and parametric tests of trend were used for analyses. Logistic regression was used to control for potential confounders and to examine effect modification between race and ethnicity and any other identified risk factors. RESULTS: During the study period, 1418 women met inclusion criteria, of whom 101 (7.1%) had a positive test result for severe acute respiratory syndrome coronavirus 2. Of the 101 women who had a positive test result, 77 (76.2%) were symptomatic at the time of diagnosis. Compared with women who had a negative test result for severe acute respiratory syndrome coronavirus 2, those with a positive test result were younger and were more likely to have public insurance, to identify as black or African American or Latina, to be unmarried, to be obese, to have preexisting pulmonary disease, and to have living children. An increasing number of living children was associated with an increasing risk of severe acute respiratory syndrome coronavirus 2 infection, and this finding persisted after controlling for potential confounders. There was no effect modification between race or ethnicity and having living children with regard to the risk of infection. There were no significant differences identified between women who were symptomatic and asymptomatic. CONCLUSION: Many risk factors for severe acute respiratory syndrome coronavirus 2 infection in pregnancy are similar to the social and structural determinants of health that have been reported in the general population. The observed association between severe acute respiratory syndrome coronavirus 2 infection and having children raises the possibility of children themselves being vectors of viral spread or behavior patterns of parents being mediators of acquisition.
Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative–sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.
Compelling evidence suggests that defective DNA damage response (DDR) plays a key role in the premature aging phenotypes in Hutchinson-Gilford progeria syndrome (HGPS). Studies document widespread alterations in histone modifications in HGPS cells, especially, the global loss of histone H3 trimethylated on lysine 9 (H3K9me3). In this study, we explore the potential connection(s) between H3K9me3 loss and the impaired DDR in HGPS. When cells are exposed to a DNA-damaging agent Doxorubicin (Dox), double strand breaks (DSBs) are generated that result in the phosphorylation of histone H2A variant H2AX (gammaH2AX) within an hour. We find that the intensities of gammaH2AX foci appear significantly weaker in the G0/G1 phase HGPS cells compared to control cells. This reduction is associated with a delay in the recruitment of essential DDR factors. We further demonstrate that ataxia-telangiectasia mutated (ATM) is responsible for the amplification of gammaH2AX signals at DSBs during G0/G1 phase, and its activation is inhibited in the HGPS cells that display significant loss of H3K9me3. Moreover, methylene (MB) blue treatment, which is known to save heterochromatin loss in HGPS, restores H3K9me3, stimulates ATM activity, increases gammaH2AX signals and rescues deficient DDR. In summary, this study demonstrates an early DDR defect of attenuated gammaH2AX signals in G0/G1 phase HGPS cells and provides a plausible connection between H3K9me3 loss and DDR deficiency.
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