Chronic exposure to gestodene impairs reproductive system in adult female zebrafish (Daniarerio).

Gestodene (GES) is widely used in human therapy and animal husbandry and is frequently detected in aquatic environments. Although GES adversely affects aquatic organisms at trace levels, its effects on the reproductive biology of fish remain inconclusive. In this study, female zebrafish (Danio rerio) were exposed to environmentally relevant levels of GES for the evaluation of the effects of GES on the reproductive system by using endpoints including gene expression, plasma steroid concentrations, histological and morphological analyses, copulatory behavior, and reproductive output. Adult female zebrafish exposed to environmentally relevant concentrations of GES (4.0, 40.2, and 372.7 ng/L) for 60 d demonstrated stagnant ovarian oocyte development, evidenced by an increase in the percentage of perinuclear and atretic oocytes and a decrease in the percentage of late vitellogenic oocytes. GES-exposed females were less attractive to males and had lower copulatory intimacy than females in control. Consequently, spawning (44.3-49.2 %) and egg fertilization rates (27.9-32.0 %) were decreased. The decreased survival of fertilized eggs and hatching rates were accompanied by increased malformations. These negative effects were associated with abnormal transcriptional levels of gonadal steroid hormones, which were regulated by genes (Hsd17ß3, Hsd11ß2, Hsd20ß, Cyp19a1a, and Cyp11b). Overall, our findings suggest that GES impairs the reproductive system of zebrafish, which may threaten population stability.

Infant Infections Following Cesarean Delivery on Maternal Request: A Population-Based Cohort Study.

OBJECTIVES: Investigations about cesarean delivery (CD) on maternal request (CDMR) and infant infection risk frequently rely on administrative data with poorly defined indications for CD. We sought to determine the association between CDMR and infant infection using an intent-to-treat approach. METHODS: This was a population-based cohort study of low-risk singleton pregnancies with a term live birth in Ontario, Canada between April 2012 and March 2018. Subjects with prior CD were excluded. Outcomes included upper and lower respiratory tract infections, gastrointestinal infections, otitis media, and a composite of these 4. Relative risk and 95% CI were calculated for component and composite outcomes up to 1 year following planned CDMR versus planned vaginal deliveries (VDs). Subgroup and sensitivity analyses included age at infection (≤28 vs. >28 days), type of care (ambulatory vs. hospitalisation), restricting the cohort to nulliparous pregnancies, and including individuals with previous CD. Last, we re-examined outcome risk on an as-treated basis (actual CD vs. actual VD). RESULTS: Of 422 134 pregnancies, 0.4% (1827) resulted in a planned CDMR. After adjusting for covariates, planned CDMR was not associated with a risk of composite infant infections (adjusted relative risk 1.02; 95% CI 0.92-1.11). Findings for component infection outcomes, subgroup, and sensitivity analyses were similar. However, the as-treated analysis of the role of delivery mode on infant risk for infection demonstrated that actual CD (planned and unplanned) was associated with an increased risk for infant infections compared to actual VD. CONCLUSIONS: Planned CDMR is not associated with increased risk for neonatal or infant infections compared with planned VD. Study design must be carefully considered when investigating the impact of CDMR on infant infection outcomes.

Why Female Smokers Have Poorer Long-Term Health Outcomes than Male Smokers: The Role of Cigarette Smoking During Pregnancy.

Objectives: Women's health status is better than men but the opposite is true for female smokers who usually have poorer long-health outcomes than male smokers. The objectives of this study were to thoroughly reviewed and analyzed relevant literature and to propose a hypothesis that may explain this paradox phenomenon. Methods: We conducted a search of literature from three English databases (EMBASE, MEDLINE, and Google Scholar) from inception to 13 November 2023. A combination of key words and/or subject headings in English was applied, including relevant terms for cigarette smoking, sex/gender, pregnancy, and health indicators. We then performed analysis of the searched literature. Results: Based on this review/analysis of literature, we proposed a hypothesis that may explain this paradox phenomenon: female smokers have worse long-term health outcomes than male smokers because some of them smoke during pregnancy, and the adverse effects of cigarette smoking during pregnancy is much stronger than cigarette smoking during non-pregnancy periods. Conclusion: Approval of our pregnancy-amplification theory could provide additional evidence on the adverse effect on women's long-term health outcomes for cigarette smoking during pregnancy.

The impact of isolated obesity compared with obesity and other risk factors on risk of stillbirth: a retrospective cohort study.

BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.

A ScWIP5 gene confers fall armyworm resistance by reducing digestive enzyme activities in sugarcane.

BACKGROUND: The fall armyworm, Spodoptera frugiperda, is one of the most dangerous pests to various crops. As the most crucial sugar crop, sugarcane is also constantly threatened by these pests. Plant wound-induced proteinase inhibitors (WIP) are natural defense proteins that play important roles in the defense system against insect attack. Breeding for resistance would be the best way to improve the variety characteristics and productivity of sugarcane. Screening and verification for potential plant endogenous insect-resistant genes would greatly improve the insect-resistant breeding progress of sugarcane. RESULTS: A sugarcane WIP5 gene (ScWIP5) was up-regulated 536 times after insect feeding treatment on previous published transcriptome databases. ScWIP5 was then cloned and its potential role in sugarcane resistance to fall armyworm evaluated by construction of transgenic Nicotiana benthamiana. The toxicity of ScWIP5 transgenic N. benthamiana to fall armyworm showed lower weight gain and higher mortality compared to wild-type N. benthamiana feeding group. Furthermore, the concentration of JA and NbAOC, NbAOS, and NbLOX from the Jasmin acid biosynthesis pathway was significantly induced in ScWIP5 transgenic N. benthamiana compared to the control. In addition, digestive enzyme actives from the insect gut were also evaluated, and trypsin and cathepsin were significantly lower in insects fed with ScWIP5 transgenic N. benthamiana. CONCLUSION: These results indicate that ScWIP5 might enhance insect resistance by increasing JA signal transduction processes and reducing insect digestive enzyme activities, thus impacting insect growth and development. © 2023 Society of Chemical Industry.

Nanocarrier-Mediated Delivery of MicroRNAs for Fibrotic Diseases.

MicroRNAs (miRNAs) are endogenous noncoding RNAs that mediate the fibrotic process by regulating multiple targets. MicroRNA-based therapy can restore or inhibit miRNA expression and is expected to become an effective approach to prevent and alleviate fibrotic diseases. However, the safe, targeted, and effective delivery of miRNAs is a major challenge in translating miRNA therapy from bench to bedside. In this review, we briefly describe the pathophysiological process of fibrosis and the mechanism by which miRNAs regulate the progression of fibrosis. Additionally, we summarize the miRNA nanodelivery tools for fibrotic diseases, including chemical modifications and polymer-based, lipid-based, and exosome-based delivery systems. Further clarification of the role of miRNAs in fibrosis and the development of a novel nanodelivery system may facilitate the prevention and alleviation of fibrotic diseases in the future.

Interpregnancy weight change and risks of stillbirth and infant mortality: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Interpregnancy weight change may impact two important adverse perinatal outcomes: stillbirth and infant mortality. This systematic review aims to synthesise the existing evidence on the association between interpregnancy weight change and stillbirth and infant mortality. METHODS AND ANALYSIS: This systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). A comprehensive literature search of four online databases (Embase, Cochrane Libraries, Web of Science and Medline) will be conducted from inception to October 2023. Observational (longitudinal, cohort, case-control) and randomised controlled trials will be included. Interpregnancy weight/body mass index change between two consecutive pregnancies will be the exposure. The primary outcomes will be the incidence of stillbirth and infant mortality in subsequent pregnancy. The Cochrane Risk of Bias tool will be used to assess the risk of bias in the randomised controlled studies and the Risk of Bias in Non-Randomised Studies of Interventions tool will be used for observational studies. If there are sufficient data, a meta-analysis will be conducted to estimate the pooled effect size. Otherwise, qualitative descriptions of individual studies will be summarised. The heterogeneity will be statistically assessed using a χ2 test and I2 statistic. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as all results will be based on published papers. No primary data collection will be needed. Study findings will be presented at scientific conferences or published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: A registration for this review has been submitted to PROSPERO under CRD42020222977.

Gestational weight loss and fetal growth in uncomplicated pregnancies among women with obesity: a population-based retrospective cohort study.

OBJECTIVE: The impact of gestational weight loss (GWL) on fetal growth among women with obesity remains unclear. This study aimed to examine the association between weight loss during pregnancy among women with body mass index (BMI) ≥ 30 kg/m2 and the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) neonates. METHODS: We conducted a retrospective, population-based cohort study of women with pre-pregnancy obesity that resulted in a singleton live birth in 2012-2017, using birth registry data in Ontario, Canada. Women with pregnancy complications or health conditions which could cause weight loss were excluded. GWL is defined as negative gestational weight change (≤0 kg). The association between GWL and fetal growth was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class (I:30-34.9 kg/m2, II:35-39.9 kg/m2, and III + : ≥40 kg/m2). RESULTS: Of the 52,153 eligible women who entered pregnancy with a BMI ≥ 30 kg/m2, 5.3% had GWL. Compared to adequate gestational weight gain, GWL was associated with an increased risk of SGA neonates (aRR:1.45, 95% CI: 1.30-1.60) and a decreased risk of LGA neonates (aRR: 0.81, 95% CI:0.73-0.93). Non-linear L-shaped associations were observed between gestational weight change and SGA neonates, with an increased risk of SGA observed with increased GWL. On the contrary, non-linear S-shaped associations were observed between gestational weight change and LGA neonates, with a decreased risk of LGA observed with increased GWL. Similar findings were observed from the stratified analysis by obesity class. CONCLUSION: These findings highlight that GWL in women with obesity may increase the risk of SGA neonates but reduce the risk of LGA neonates. Recommendations of GWL for women with obesity should be interpreted with caution.

Effects of norethindrone on the growth, behavior, and thyroid endocrine system of adult female western mosquitofish (Gambusia affinis).

Progestins are mainly used in pharmacotherapy and animal husbandry and have received increasing attention as they are widely detected in various aquatic ecosystems. In this study, adult female western mosquitofish (Gambusia affinis) were exposed to different concentrations of norethindrone (NET) (solvent control, 5.0 (L), 50.0 (M), and 500.0 (H) ng/L) for 42 days. Behaviors, morphological parameters, histology of the thyroid, thyroid hormone levels (TSH, T3, and T4), and transcriptional levels of nine genes in the hypothalamic-pituitary-thyroid (HPT) axis were examined. The results showed that NET decreased sociality but increased the anxiety of G. affinis. Sociality makes fish tend to cluster, and anxiety may cause G. affinis to reduce exploration of new environments. Female fish showed hyperplasia, hypertrophy, and glial depletion in their thyroid follicular epithelial cells after NET treatment. The plasma levels of TSH and T4 were significantly reduced, but T3 concentrations were significantly increased in the fish from the H group. In addition, the transcripts of genes (tshb, tshr, tg, dio1, dio2, thrb) in the brains of fish in the M and H treatments were significantly stimulated, while those of trh and pax2a were suppressed. Our results suggest that NET may impact key social behaviors in G. affinis and interfere with the entire thyroid endocrine system, probably via affecting the transcriptional expression of upstream regulators in the HPT axis.

Chronic exposure to cortisone induces thyroid endocrine disruption and retinal dysfunction in adult female zebrafish (Danio rerio).

Cortisone has a large content in rivers because of its wide range of medical applications and elimination by organisms that naturally secrete it. As a steroid hormone, cortisone is recognized as a novel endocrine disruptor. Although ecotoxicological effects of the reproductive endocrine system have mainly been reported recently, thyroid endocrine in fish remains relatively less understood. Here, adult female zebrafish were exposed to cortisone at 0.0 (control), 3.2, 38.7, and 326.9 ng/L for 60 days. Evidence in this study came from fish behavior, hormone levels, gene expression, histological and morphological examinations. The results showed that THs (thyroid hormone) level disruption and pathohistological changes occurred in the thyroid gland, which may account for the gene expression changes in the hypothalamus-pituitary-thyroid gland axis. Specifically, more conversion of T4 (thyroxine) to T3 (triiodothyronine) led to an increased TSH (thyroid stimulating hormone) level in plasma. Severe thyroid tissue damage mainly occurred in the zebrafish exposed to 326.9 ng/L of cortisone. Meanwhile, consistent with the THs trend, the fish locomotion activity displayed more anxiety and excitement, the partial blockage of GABA (γ - aminobutyric acid) synthetic pathway genes might be the explanation of the underlying mechanism. Cortisone affected the gene expressions in the visual cycle and the circadian rhythm network also suggested interactions between thyroid endocrine disruption, retinal dysfunction, and abnormal behaviors of zebrafish. In summary, these findings suggest chronic exposure to cortisone induced various adverse effects in adult female zebrafish, which may help us better understand the risk of cortisone to fish in the wild.

Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation.

BACKGROUND: Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. OBJECTIVES: The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. DESIGN: This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011-2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). RESULTS: There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68-4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74-3.38), and hypertension (ARR:1.92, 95% CI: 1.37-2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15-7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62-4.67), and hypertension (ARR:2.18, 95% CI:1.28-3.72). No significant differences were found for obesity or diabetes. CONCLUSION: These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis).

The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4.4-378.7 ng/L) for 60 days. The results showed that exposure to 378.7 ng/L GES caused a significant decrease in fish growth compared with the control and a marked reduction in the total distance traveled (50.6%) and swimming velocity (40.1-61.9%). The triiodothyronine (T3) levels were significantly increased by GES in a dose-dependent manner, whereas those of tetraiodothyronine (T4) were significantly decreased only at the G500 concentration. The acetylcholinesterase (AChE) activity was decreased significantly in the 4.42 ng/L GES treatments, but increased significantly at 378.67 ng/L. In the brain, a strong increase in the transcriptional levels of bdnf, trh, and dio2 was observed in fish after the 378.7 ng/L treatment. In addition, chronic exposure to GES caused colloid depletion with a concentration-dependent manner in the thyroid, and angiectasis, congestion, and vacuolar necrosis in the brain. These findings provide a better understanding of the effects of GES and associated underlying mechanisms in G. affinis.

The ubiquitin-proteasome system in melanin metabolism.

BACKGROUND: The ubiquitin-proteasome system (UPS) is a highly conserved way of regulating intracellular protein balance. UPS mediates proteolysis and disruption of variation or misfolding, while finely regulating proteins involved in differentiation and other biological processes. AIMS: The aim of this review is to systematically introduce UPS as a key regulator of melanin metabolism. METHODS: Systematic search and retrospective review were performed on the published data. RESULTS: Melanocyte-inducing transcription factor (MITF) is a substrate of the ubiquitin ligase VCHL1 and acts as a transcription factor to regulate the expression of key enzymes in melanin synthesis such as tyrosinase (TYR). The rate-limiting enzyme TYR is modified by the ubiquitin ligase Hrd1 during melanosynthesis. Melanin itself is also regulated by multiple ubiquitin ligases including Fbp1 and Vhl. By regulating the ubiquitination modification to target each link of melanin synthesis, it plays an important role in correcting the disorder of melanin metabolism. A number of chemical agents have been proven to inhibit the activity of ubiquitin ligase. CONCLUSIONS: Drugs targeting E3 ligase and deubiquitinating enzymes have great potential in the treatment of melanin metabolism disorders.

Recombinant Plasminogen Activator Modified Nanoparticles for Targeting Thrombolysis in Branch Retinal Vein Occlusion.

Branch Retinal Vein Occlusion (BRVO) is the second chronic branch retinal vascular disease that causes abnormal vision loss after acute branch retinal disease in type 2 diabetes. There is no scientific conclusion about its specific pathogenic mechanism at present. Most clinical scholars generally support the theory that the partial human anatomical structure and various systemic risk psychological factors cause insufficient oxygen supply and hemostasis in the local branch retinal arteries. The research results of this article aim to reconstruct a non-nanocell-targeted thrombolytic drug delivery system without modification of rtPA without polyethylene glycol-methyl polycaprolactone and to re-evaluate its thrombus targeting and dissolution. The effect and safety of thrombus provide a new strategy for realizing combined treatment of thrombus. It is a study on the targeting of rtPA-NP to thrombus and its thrombolytic properties. HPLC method was used to detect the binding of fibrin clot prepared in vitro with coumarin-6 labeled NP and rtPA-NP; immunofluorescence technique was used to observe the location of nanomedicine and fibrin clot in branch retinal vein occlusion model Condition. The rtPA-NP drug delivery system constructed in this study not only retains the activity of rtPA and good thrombus targeting but also significantly prolongs its half-life and simplifies the way of administration. The therapeutic efficiency of rtPA-NP thrombus targeted administration on branch retinal vein occlusion reached 85.64%. The successful construction of the rtPA-NP thrombus targeted drug delivery system provides a new way for thrombosis treatment and lays the foundation for the future combination of anticoagulants and vascular protection drugs to achieve the combined treatment of thrombosis and the development of safe and efficient thrombolytic drugs.

A MDM2 inhibitor MX69 inhibits adipocytes adipogenesis and differentiation.

Adipose tissue, a key regulator of systemic energy homeostasis, can synthesize and store triglycerides to meet long-term energy demands. In response to nutrient overload, adipose tissue expands by hypertrophy or hyperplasia. As an oncogene, MDM2 has exerted diverse biological activities including human development, tissue regeneration, and inflammation, in addition to major oncogenic activities. Recently, some studies indicated that MDM2 plays an important role in adipose tissue function. However, the role of MX69, a MDM2 inhibitor, in adipose tissue function has not been fully elucidated. Here, we administered MX69 intraperitoneally to high-fat diet-induced obesity (DIO) wild type C57BL/6 mice and found that MX69 could promote the body weight and white adipose tissue weight of DIO mice. Moreover, MX69 had no effects on glucose tolerance and insulin sensitivity in DIO mice. And MX69 treatment decreased the size of adipocytes and fat deposition in adipose tissue and inhibited 3T3-L1 preadipocytes differentiation. Mechanistically, MX69 inhibited the protein levels of MDM2 and the mRNA levels of genes related to adipogenesis and differentiation. In summary, our results indicated that MDM2 has a crucial and complex role in regulating adipose tissue function.

Impact of COVID-19 pandemic on emergency department visits and infant health: a scoping review protocol.

INTRODUCTION: The novel SARS-CoV-2 pandemic has provided a set of unique challenges for paediatric patients requiring emergency care across the globe. Reduction in paediatric emergency department (ED) usage during the COVID-19 pandemic has been widely reported, but no studies to date have consolidated and described what ramifications these reductions may have on neonatal and infant health. This scoping review aims to characterise the impact of the COVID-19 pandemic on infant ED visits and neonatal and infant health. METHODS AND ANALYSIS: A comprehensive literature search will be conducted from March 2020 to July 2022 using the following databases: Embase (Ovid), Web of Science (Clarivate Analytics), Medline (Ovid) and CINAHL (EBSCOhost). This scoping review will use a five-step framework to guide the selection, extraction and analysis of data from eligible studies, with an additional sixth step for clinical consultation. Studies in English reporting the effect of the COVID-19 pandemic on infant ED visits, as well as neonatal and infant health, will be included for screening. Key findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. ETHICS AND DISSEMINATION: Research ethics board approval will not be required due to the nature of the study design. The results of this scoping review will be disseminated through publication in a peer-reviewed journal and presentation at academic conferences.

Giving Birth in the Early Phases of the COVID-19 Pandemic: The Patient Experience.

OBJECTIVE: Obstetrical patients are at risk of complications from COVID-19 and face increased stress due to the pandemic and changes in hospital birth setting. The objective was to describe the perinatal care experiences of obstetrical patients who gave birth during the early phases of the COVID-19 pandemic. METHODS: A descriptive epidemiological survey was administered to consenting patients who gave birth at The Ottawa Hospital (TOH) between March 16th and June 16th, 2020. The participants reported on prenatal, in-hospital, and postpartum care experiences. COVID-19 pandemic related household stress factors were investigated. Frequencies and percentages are presented for categorical variables and median and interquartile range (IQR) for continuous variables. RESULTS: A total of 216 participants were included in the analyses. Median participants age was 33 years (IQR: 30-36). Collectively, 94 (43.5%) participants felt elevated stress for prenatal appointments and 105 (48.6%) for postpartum appointments because of COVID-19. There were 108 (50.0%) were scared to go to the hospital for delivery, 97 (44.9%) wore a mask during labour and 54 (25.0%) gave birth without a support person. During postpartum care, 125 (57.9%) had phone appointments (not offered prior to COVID-19), and 18 (8.3%) received no postpartum care at all. CONCLUSION: COVID-19 pandemic and public health protocols created a stressful healthcare environment for the obstetrical population where many were fearful of accessing services, experienced changes to standard care, or no care at all. As the pandemic continues, careful attention should be given to the perinatal population to reduce stress and improve continuity of care.

RéSUMé: OBJECTIF: Les patients obstétriques sont à risque de complications de la COVID-19 et font face à un stress accru en raison de la pandémie et des changements dans le cadre de l'accouchement en milieu hospitalier. L'objectif était de décrire les expériences de soins périnataux des patients obstétriques qui ont accouché au cours des premières phases de la pandémie de COVID-19. MéTHODES: Un sondage épidémiologique descriptif a été menée auprès de patients qui ont accouché à L'Hôpital d'Ottawa (TOH) entre le 16 mars et le 16 juin 2020. Les participants ont fait un compte rendu de leurs expériences en matière de soins prénataux, hospitaliers et post-partum. Les facteurs de stress domestique liés à la COVID-19 ont été étudiés. Les fréquences et les pourcentages sont présentés pour les variables catégorielles et la médiane et l'écart interquartile (IQR) sont présentés pour les variables continues. RéSULTATS: Au total, 261 participants ont répondu au sondage. L'âge maternel médian était de 33 ans (IQR: 30­36). Collectivement, 94 participants (43,5%) ressentaient un stress élevé en lien avec les rendez-vous prénataux et 105 (48,6%) pour les rendez-vous post-partum en raison de la COVID-19. Il y avait 108 patients (50,0%) qui avaient peur d'aller à l'hôpital pour accoucher, 97 (44,9%) qui portaient un masque pendant leur travail et 54 (25,0%) qui ont accouché sans personne de soutien. En lien avec les soins post-partum, 125 (57,9%) ont eu des rendez-vous téléphoniques (non offerts avant la pandémie COVID-19) et 18 (8,3%) n'ont reçu aucun soin post-partum. CONCLUSION: La pandémie de COVID-19 et les politiques de santé publique ont créé un environnement de soins de santé stressant pour la population obstétrique où beaucoup avaient peur d'accéder aux services de soins, ont connu des changements dans les soins de base ou n'ont pas eu de soins du tout. Alors que la pandémie se poursuit, une attention particulière doit être accordée à la population périnatale afin de réduire le stress et améliorer la continuité des soins.

Murine double minute 2 aggravates adipose tissue dysfunction through ubiquitin-mediated six-transmembrane epithelial antigen of prostate 4 degradation.

Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. Mdm2 adipocyte-specific knock-in (Mdm2-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in Mdm2-AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of Mdm2-AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis.

Racial variations of adverse perinatal outcomes: A population-based retrospective cohort study in Ontario, Canada.

INTRODUCTION: Racial differences in adverse maternal and birth outcomes have been studied in other countries, however, there are few studies specific to the Canadian population. In this study, we sought to examine the inequities in adverse perinatal outcomes between Black and White pregnant people in Ontario, Canada. METHODS: We conducted a population-based retrospective cohort study that included all Black and White pregnant people who attended prenatal screening and had a singleton birth in any Ontario hospital (April 1st, 2012-March 31st, 2019). Poisson regression with robust error variance models were used to estimate the adjusted relative risks of adverse perinatal outcomes for Black people compared with White people while adjusting for covariates. RESULTS: Among 412,120 eligible pregnant people, 10.1% were Black people and 89.9% were White people. Black people were at an increased risk of gestational diabetes mellitus, preeclampsia, placental abruption, preterm birth (<37, <34, <32 weeks), spontaneous preterm birth, all caesarean sections, emergency caesarean section, low birth weight (<2500g, <1500g), small-for-gestational-age (<10th percentile, <3rd percentile) neonates, 5-minute Apgar score <4 and <7, neonatal intensive care unit admission, and hyperbilirubinemia requiring treatment but had lower risks of elective caesarean section, assisted vaginal delivery, episiotomy, 3rd and 4th degree perineal tears, macrosomia, large-for-gestational-age neonates, and arterial cord pH≤7.1, as compared with White people. No difference in risks of gestational hypertension and placenta previa were observed between Black and White people. CONCLUSION: There are differences in several adverse perinatal outcomes between Black and White people within the Ontario health care system. Findings might have potential clinical and health policy implications, although more studies are needed to further understand the mechanisms.

An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression.

Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958 individuals and identify rs73613962 (T > G) within the intronic region of PRMT7 at 16q22.1 as a susceptibility locus of HCC (OR = 1.41, P = 6.02 × 10-10). An enhancer dual-luciferase assay indicates that the rs73613962-harboring region has allele-specific enhancer activity. CRISPR-Cas9/dCas9 experiments further support the enhancer activity of this region to regulate PRMT7 expression. Mechanistically, transcription factor HNF4A binds to this enhancer region, with preference to the risk allele G, to promote PRMT7 expression. PRMT7 upregulation contributes to in vitro, in vivo, and clinical HCC-associated phenotypes, possibly by affecting the p53 signaling pathway. This concept of HCC pathogenesis may open a promising window for HCC prevention/treatment.