Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs. Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation. Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05). Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Giant mucinous cystadenocarcinoma of ovary in a young woman: a case report and review of literature.

In April 2023, we successfully treated a 21-year-old patient afflicted with a rare giant cystadenocarcinoma, an extraordinarily large mucinous ovarian tumor that weighed nearly 25 kg. The preoperative dimensions of the tumor measured 40 × 30 × 34 cm, with the tumor's weight nearing 25 kg. Despite its uncommon nature, we elected to perform a right adnexectomy, greater omentectomy, and peritoneal biopsy during the surgical intervention due to the patient's youth and the family's expressed desire to preserve fertility. In the subsequent August follow-up, CT scans revealed the complete resolution of the tumor, accompanied by the normalization of tumor markers, indicating a favorable outcome.

Long-Acting Reversible Contraception Knowledge Among Female Adolescents Presenting to a Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to assess awareness and use of long-acting reversible contraception (LARC) among female adolescents presenting to a pediatric emergency department (PED). STUDY DESIGN: During routine presentation to an urban PED in New Jersey, female adolescents, aged 15-19 years, were asked to voluntarily complete an electronic survey about sexual practices and contraception. The PED is in an urban teaching hospital, treating 35,000 children annually. Patients could schedule a follow-up appointment at the hospital's obstetrics/gynecology clinic. Data were collected over 13 months, and follow-up was monitored to determine if they attended an outpatient appointment, and if so, what the outcome was. RESULTS: Data for 199 participants were analyzed. The median age of participants was 18 years, whereas 79% self-identified as Black, and 17.6% self-identified as Latina. Twenty-one percent of participants used a form of birth control during their first sexual encounter, the largest percentage being condoms (77.8%). Forty percent of participants reported some prior knowledge about contraceptive implants, and 20% had knowledge about intrauterine devices, whereas only 3 (1.5%) intrauterine devices and 2 (1%) arm implants had been previously used. Of the 78 participants that requested a follow-up, 14 (17.9%) completed their appointment. Of those, 2 (14%) were prescribed contraception (Depo-Provera shot and oral contraceptive pills). CONCLUSIONS: Knowledge about LARC remains low in our PED, despite it being the most effective method of contraception. Even when interventions were made to link interested respondents to outpatient women's health services, follow-up attendance was poor, and no patients obtained LARC. There is a significant discrepancy between the consensus standard of contraception care across all relevant medical specialties and current utilization by high-risk populations. Future efforts must focus on how to close this gap, and the ED could be pivotal for improving both reproductive health education and intervention among adolescent patients.

PFAS Exposures and the Human Metabolome: A Systematic Review of Epidemiological Studies.

Purpose of Review: There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines. Recent Findings: We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional (n = 25), including four with prospective analyses of PFAS measured prior to metabolomics. Summary: Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.

The Impact of Surgical Boot Camp on Medical Student Confidence and Imposter Syndrome.

INTRODUCTION: Transitioning from medical student to surgical intern is accompanied by increased responsibility, stress, and clinical burden. This environment lends itself to imposter syndrome (IS), a psychological condition grounded in self-doubt causing fear of being discovered as fraud despite adequate abilities. We hypothesized a 2-week surgical boot camp for fourth year medical students would improve confidence in technical skills/knowledge and IS. METHODS: Thirty medical students matching into surgical specialties completed the boot-camp in February 2020. Presurveys/postsurveys assessed confidence levels using a 1-5 Likert scale regarding 32 technical skills and knowledge points. The Clance Impostor Phenomenon Scale (CIPS) assessed IS, where increasing scores correlate to greater IS. RESULTS: Median (interquartile range [IQR]) subject age was 27 y (26, 28), 20 (66.7%) were male, and 21 (70%) were Caucasian. Of the 30 students, 23 (76.7%) had a break in training with a median [IQR] of 2 [1, 3] y outside of medicine. Confidence scores were significantly improved in all five assessment categories (P < 0.05); however, there was no change in CIPS in median [IQR] presurveys versus postsurveys (65.5 [52, 75] versus 64 [52, 75], P = 0.70). Females had higher mean (standard deviation) pre-CIPS than males (68.4 [15.2] versus 61.6 [14.9], P = 0.02). There was no strong correlation between age and CIPS in the presurvey (Spearman Rank Correlation Coefficient [SRCC]: 0.29, P = 0.19) or postsurvey (SRCC: 0.31, P = 0.10). While subjects who worked outside of medicine had a stronger relationship with IS (SRCC: 0.37, P = 0.05), multivariable regression analysis did not reveal any significant differences. CONCLUSIONS: We advocate for surgical boot-camp training courses to improve trainee skill and confidence. As IS is not improved by boot camp, additional research is needed to identify opportunities to improve IS among surgical trainees.

Exposure to perfluoroalkyl substances and women's fertility outcomes in a Singaporean population-based preconception cohort.

OBJECTIVES: Experimental models have demonstrated a link between exposure to perfluoroalkyl substances (PFAS) and decreased fertility and fecundability; however, human studies are scarce. We assessed the associations between preconception plasma PFAS concentrations and fertility outcomes in women. METHODS: In a case-control study nested within the population-based Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO), we measured PFAS in plasma collected in 2015-2017 from 382 women of reproductive age trying to conceive. Using Cox proportional hazards regression (fecundability ratios [FRs]) and logistic regression (odds ratios [ORs]) models, we assessed the associations of individual PFAS with time-to-pregnancy (TTP), and the likelihoods of clinical pregnancy and live birth, respectively, over one year of follow-up, adjusting for analytical batch, age, education, ethnicity, and parity. We used Bayesian weighted quantile sum (BWQS) regression to assess the associations of the PFAS mixture with fertility outcomes. RESULTS: We found a 5-10 % reduction in fecundability per quartile increase of exposure to individual PFAS (FRs [95 % CIs] for clinical pregnancy = 0.90 [0.82, 0.98] for PFDA; 0.88 [0.79, 0.99] for PFOS; 0.95 [0.86, 1.06] for PFOA; 0.92 [0.84, 1.00] for PFHpA). We observed similar decreased odds of clinical pregnancy (ORs [95 % CIs] = 0.74 [0.56, 0.98] for PFDA; 0.76 [0.53, 1.09] for PFOS; 0.83 [0.59, 1.17] for PFOA; 0.92 [0.70, 1.22] for PFHpA) and live birth per quartile increases of individual PFAS and the PFAS mixture (ORs [95 % CIs] = 0.61 [0.37, 1.02] for clinical pregnancy, and 0.66 [0.40, 1.07] for live birth). Within the PFAS mixture, PFDA followed by PFOS, PFOA, and PFHpA were the biggest contributors to these associations. We found no evidence of association for PFHxS, PFNA, and PFHpS and the fertility outcomes examined. CONCLUSIONS: Higher PFAS exposures may be associated with decreased fertility in women. The potential impact of ubiquitous PFAS exposures on infertility mechanisms requires further investigation.

Prenatal Metal Exposures and Associations with Kidney Injury Biomarkers in Children.

Prenatal exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) may be nephrotoxic, yet limited studies have examined subclinical kidney injury biomarkers in children. We assessed whether metal exposure in the second trimester (2T), a crucial time of kidney development, is associated with altered urine kidney injury and function biomarkers in preadolescent children. Analyses included 494 children participating in a birth cohort study in Mexico City. Concentrations of As, Cd, and Pb were measured from pregnant women in 2T blood and urine, and Hg in urine only. Kidney biomarkers were measured from children in urine at age 8-12 years. We assessed the associations between individual metals and (1) kidney biomarkers using linear regression and (2) a multi-protein kidney mixture using weighted quantile sum (WQS) regression. Associations of separate urine and blood metal mixtures with individual kidney biomarkers were assessed via WQS. Within the multi-protein mixture, the association with increased urinary As was predominated by urine alpha-1-microglobulin (A1M), interferon gamma-induced protein 10 (IP10), and fatty acid binding protein 1; the association with increased urinary Cd was predominated by A1M, clusterin, and albumin. The urine metal mixture was associated with increased albumin (0.23 ng/mL; 95% confidence interval (CI): 0.10, 0.37), IP10 (0.15 ng/mL; 95% CI: 0.02, 0.28), and cystatin C (0.17 ng/mL; 95% CI: 0.04, 0.31); these associations were mainly driven by urinary As and Cd. We observed null associations between prenatal blood or urine metal mixtures and estimated glomerular filtration rate. Higher prenatal urinary metals, individually and as a mixture were associated with altered kidney injury biomarkers in children. Further research and longer participant follow-up are required to ascertain the risk of kidney disease later in life.

Estimating the Nosocomial Transmission Rate of COVID-19 in Orthopaedic Surgery Patients During the Peak of the Pandemic.

Purpose: To estimate the risk of hospital-acquired COVID-19 transmission in a population of orthopaedic trauma patients during the first wave of the pandemic. Patients and Methods: This is a retrospective cohort study of 109 patients who underwent an emergent orthopedic procedure by a single orthopedic traumatologist between March 1, 2020 and May 15, 2020 during the first peak of the pandemic. After applying inclusion and exclusion criteria, a total of 82 patients (67 inpatients and 15 ambulatory) were identified for final analysis. The primary outcome measured was postoperative Coronavirus (COVID-19) status. Secondary outcome measures included length of stay and discharge disposition. Results: The mean age and length of stay in the hospital group was 59.5 years (± 21.7) and 4.3 days (± 4.6), respectively, versus 47.9 years (± 9.8) in the ambulatory group. 7.3% (6/82) of the inpatients subsequently tested or screened positive for COVID-19 at 2 weeks post-operatively, compared to 0/15 ambulatory patients (P=0.58). Of the 6 inpatients who tested positive, 4 (66.7%) were discharged to a rehabilitation center. Diabetes (P=0.05), hypertension (P=0.02), and congestive heart failure (P=0.005) were associated with transmission. Conclusion: In this analysis, there was a nosocomial transmission rate of 7% compared to zero in the ambulatory surgery center, however this was not found to be statistically significant. This data supports the use of precautions such as frequent screening, hand washing, and masks to reduce transmission when COVID-19 rates are high. There is a lower risk of nosocomial COVID-19 transmission for patients treated as an outpatient and elective surgical procedures may be safer in this setting.

LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR-186-5p/ZEB1 axis.

LncRNA TUG1 has been rarely studied in ovarian cancer (OC), our objective was to explore the role of TUG1 in the regulation of malignant phenotypes of OC. Vectors of sh-TUG1, miR-186-5p and pcDNA-ZEB1 were, respectively, constructed and used to infect OC cells. MTT and transwell assays were applied for representing cell proliferation and invasion, respectively. Sphere formation experiment was used to detect the stemness of OC cells. Western blotting and qRT-PCR were employed for detecting the expression of multiple biomarkers on protein and RNA levels, respectively. The luciferase assay was performed to reveal the interactions between miR-186-5p and TUG1 or ZEB1. The silencing of TUG1 and upregulation of miR-186-5p both suppressed the cell proliferation, invasion and cancer stem cell (CSC) properties. Additionally, luciferase assay verified that miR-186-5p directly binds TUG1 and ZEB1. Moreover, overexpression of ZEB1 rescued the impact on the proliferation, invasion and stemness of TUG1 silencing in OC. TUG1 sponges miR-186-5p to release ZEB1 and promotes the proliferation, invasion and stemness of OC cells, suggesting that TUG1 could be a potential therapeutic target for OC therapy. SIGNIFICANCE OF THE STUDY: LncRNA TUG1 could promote proliferation, invasion and stemness of ovarian cancer cells. Our study first discovered that TUG1 play a tumourigenic role in ovarian cancer by regulating stemness of cancer cells. Mechanism research exhibited the regulation role of TUG1 in ovarian cancer cells was miR-186-5p/ZEB1 axis depended. These results provided a new perspective to understand the pathogenesis and development of ovarian cancer; it will offer new evidence for better diagnosis and treatment therapy of ovarian cancer.

SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2.

Staphylococcal nuclease domain-containing protein 1 (SND1) is known to be involved in the progression of a variety of human cancers. However, the role of SND1 in cervical cancer remains unclear. Here, we found that the expression of SND1 in cervical cancer tissue was higher than that in normal cervical tissue. Importantly, high SND1 expression was closely associated with tumorigenic phenotype and shorter survival among cervical cancer patients. Functional assays demonstrated that SND1 knockdown inhibited the migration and invasion capabilities of cervical cancer cells in vitro. Additionally, a xenograft assay showed that silencing SND1 in cervical cancer cells suppressed lung metastasis in vivo. Further investigation revealed that knockdown of SND1 inhibited epithelial-to-mesenchymal transition (EMT) of cervical cancer cells by enhancing FOXA2 expression. Moreover, the pro-metastasis effect of SND1 in cervical cancer was at least in part dependent on FOXA2 inhibition. Mechanistically, we found that SND1-induced FOXA2 ubiquitination resulted in degradation, mediated by the E3 ligase enzyme Smurf1. In summary, SND1 plays a crucial role in cervical cancer metastasis, and we provide evidence that SND1 may serve as a prognostic and therapeutic target in cervical cancer.