Maternal loss-of-function of Nlrp2 results in failure of epigenetic reprogramming in mouse oocytes.

Background: NLRP2 belongs to the subcortical maternal complex (SCMC) of mammalian oocytes and preimplantation embryos. This multiprotein complex, encoded by maternal-effect genes, plays a pivotal role in the zygote-to-embryo transition, early embryogenesis, and epigenetic (re)programming. The maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans. However, the underlying molecular mechanisms for the diverse functions of the SCMC, particularly how this cytoplasmic structure influences DNA methylation, which is a nuclear process, are not fully understood. Results: We undertook joint transcriptome and DNA methylome profiling of pre-ovulatory germinal-vesicle oocytes from Nlrp2-null, heterozygous (Het), and wild-type (WT) female mice. We identified numerous differentially expressed genes (DEGs) in Het and Nlrp2-null when compared to WT oocytes. The genes for several crucial factors involved in oocyte transcriptome modulation and epigenetic reprogramming, such as DNMT1, UHRF1, KDM1B and ZFP57 were overexpressed in Het and Nlrp2-null oocytes. Absence or reduction of Nlrp2, did not alter the distinctive global DNA methylation landscape of oocytes, including the bimodal pattern of the oocyte methylome. Additionally, although the methylation profile of germline differentially methylated regions (gDMRs) of imprinted genes was preserved in oocytes of Het and Nlrp2-null mice, we found altered methylation in oocytes of both genotypes at a small percentage of the oocyte-characteristic hyper- and hypomethylated domains. Through a tiling approach, we identified specific DNA methylation differences between the genotypes, with approximately 1.3% of examined tiles exhibiting differential methylation in Het and Nlrp2-null compared to WT oocytes. Conclusions: Surprisingly, considering the well-known correlation between transcription and DNA methylation in developing oocytes, we observed no correlation between gene expression differences and gene-body DNA methylation differences in Nlrp2-null versus WT oocytes or Het versus WT oocytes. We therefore conclude that post-transcriptional changes in the stability of transcripts rather than altered transcription is primarily responsible for transcriptome differences in Nlrp2-null and Het oocytes.

Endometrial receptivity array before frozen embryo transfer cycles: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of endometrial receptivity array (ERA) before frozen embryo transfer in patients undergoing in vitro fertilization (IVF). There is a lack of consensus regarding the use of ERA for increasing the success rate of IVF cycles, mainly in terms of the live birth rate. DESIGN: PubMed, Web of Science and Embase were searched from inception up to February 15, 2022. SETTING: Not applicable. PATIENT(S): Patients undergoing ERA vs no ERA before frozen embryo transfer. INTERVENTION(S): Only comparative studies evaluating pregnancy rates of patients undergoing frozen embryo transfer cycles with or without prior ERA were included. Inter-study heterogeneity was also assessed using Cochrane's Q test and the I2 statistic. The random-effects model was used to pool the odds ratio (OR) with the corresponding 95% confidence intervals (CIs). Subgroup analyses were performed to investigate the impact of ERA on pregnancy rates according to the number of previous embryo transfer (ET) failures (≤ 2 previous failed ETs vs. > 2 failed ETs, defined as recurrent implantation failure). Separate analyses were performed according to the study design and adjustment for confounders. MAIN OUTCOME MEASURES(S): The primary outcomes of the study were live birth rate and/or ongoing pregnancy rate. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate were considered secondary outcomes. RESULT(S): Eight studies (representing data on n = 2,784 patients; n = 831 had undergone ERA and n = 1,953 without ERA) were found to be eligible for this meta-analysis. The live birth or ongoing pregnancy rate for the ERA group was not significantly different compared with the non-ERA group (OR, 1.38; 95% CI, 0.79-2.41; I2 83.0%), nor was a difference seen in subgroup analyses based on the number of previous failed ETs. The rates of implantation, biochemical pregnancy, clinical pregnancy, and miscarriage were also comparable between the ERA and the non-ERA groups. After separate analyses according to the study design and adjustment for confounding factors, overall pooled estimates remained statistically nonsignificant. CONCLUSION(S): The findings of the current meta-analysis did not reveal a significant change in the rate of pregnancy after IVF cycles using ERA, and it is not clear whether ERA can increase the pregnancy rate or not. SYSTEMATIC REVIEW REGISTRATION: Prospectively registered in PROSPERO (CRD42022310862).

Imaging for acute appendicitis at nonpediatric centers exposes children to excess radiation.

BACKGROUND: Radiation exposure is the reason for the decreased utilization of computed tomography (CT) in pediatric centers (PCs). We sought to compare the radiation dose exposure of CT imaging performed at outside hospitals (OH) versus PC in pediatric patients with acute appendicitis (AA). MATERIAL AND METHODS: A retrospective review of all patients managed at our PC for AA from January 2011 to March 2016 was performed. Patients who had CT imaging for AA at OH were compared to those who underwent CT for appendicitis at our PC. Radiation dosing was compared using the dose index (CTDI [mGY]) and dose length product (DLP [mGYcm]). Independent t-test samples were used to compare means for radiation dose. RESULTS: 379 patients met inclusion criteria. There were 59.4% (225) patients imaged at our PC and 40.6% (154) patients were transferred from an OH. When performed at OH, 6.5% of CTs were considered inadequate as they were done without intravenous contrast compared to 1.3% in our PC. Mean CTDI was 6.9 at our PC and 11.8 at OH (P < 0.0001). Mean DLP at PC was 296.2 versus 456.8 at OH (P < 0.0001). An excess radiation dose of 4.9 mGY and 160.5 mGYcm was noted when CT scan was performed at OH versus PC. CONCLUSIONS: Using DLP as a gauge of radiation exposure, CT imaging performed at OH has a 44% higher radiation rate relative to the exposure at PC. In cases of suspected AA at a facility without pediatric surgeons, early transfer to PC prior to imaging is advocated.

Risk Factors for Inpatient Hospital Admission in Pediatric Burn Patients.

PURPOSE: Our objective was to determine the risk factors for inpatient admission of pediatric burn patients. MATERIALS & METHODS: This cross-sectional study uses data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUP KID) for the years of 2003, 2006, 2009, and 2012 to estimate the risk factors for inpatient admission for pediatric patients who sustained a burn injury. Patients who sustained a burn between the ages of 1 and 18 years were included. RESULTS: A total of 43,453 patients met inclusion criteria. Of those, 42.3% were Caucasian, 20.1% were African American, and 19.3% were Hispanic. Males comprised 63.5% of the studied population. The month of July was associated with a 31.8% increased chance (p=.011) of being admitted to hospital for a pediatric burn. It was found that patients being admitted had a 32.2% increased chance (p=.002) of a fluid and electrolyte abnormality and a 61.0% increased chance (p=.027) of drug abuse. CONCLUSIONS: Pediatric burn patients are more likely to be admitted to the hospital having a fluid and electrolyte abnormality, having a drug abuse status, and/or during the month of July.

Pediatric Trauma Transfer Imaging Inefficiencies-Opportunities for Improvement with Cloud Technology.

BACKGROUND: This study examines the inefficiencies of radiologic imaging transfers from one hospital to the other during pediatric trauma transfers in an era of cloud based information sharing. METHODS: Retrospective review of all patients transferred to a pediatric trauma center from 2008-2014 was performed. Imaging was reviewed for whether imaging accompanied the patient, whether imaging was able to be uploaded onto computer for records, whether imaging had to be repeated, and whether imaging obtained at outside hospitals (OSH) was done per universal pediatric trauma guidelines. RESULTS: Of the 1761 patients retrospectively reviewed, 559 met our inclusion criteria. Imaging was sent with the patient 87.7% of the time. Imaging was unable to be uploaded 31.9% of the time. CT imaging had to be repeated 1.8% of the time. CT scan was not done per universal pediatric trauma guidelines 1.2% of the time. CONCLUSION: Our study demonstrated that current imaging transfer is inefficient, leads to excess ionizing radiation, and increased healthcare costs. Universal implementation of cloud based radiology has the potential to eliminate excess ionizing radiation to children, improve patient care, and save cost to healthcare system.