Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation.

Heparan sulfate (HS) regulation of FGFR function, which is essential for salivary gland (SG) development, is determined by the immense structural diversity of sulfated HS domains. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS), and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs) that produce basement membrane (BM) and are a growth factor signaling hub. Hs3st3a1;Hs3st3b1 double-knockout (DKO) mice generated to investigate 3-O-HS regulation of MEC function and growth factor signaling show loss of specific highly 3-O-HS and increased FGF/FGFR complex binding to HS. During development, this increases FGFR-, BM- and MEC-related gene expression, while in adult, it reduces MECs, increases BM and disrupts acinar polarity, resulting in salivary hypofunction. Defined 3-O-HS added to FGFR pulldown assays and primary organ cultures modulates FGFR signaling to regulate MEC BM synthesis, which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.

Effect of an Intrapartum Pelvic Dilator Device on Levator Ani Muscle Avulsion During Primiparous Vaginal Delivery: A Pilot Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the safety and effectiveness of an intrapartum electromechanical pelvic floor dilator designed to reduce the risk of levator ani muscle (LAM) avulsion during vaginal delivery. METHODS: A multicenter, randomized controlled trial enrolled nulliparous participants planning vaginal delivery. During the first stage of labor, participants were randomized to receive the intravaginal device or standard-of-care labor management. The primary effectiveness endpoint was the presence of full LAM avulsion on transperineal pelvic-floor ultrasound at 3 months. Three urogynecologists performed blinded interpretation of ultrasound images. The primary safety endpoint was adverse events (AEs) through 3 months. RESULTS: A total of 214 women were randomized to Device (n = 113) or Control (n = 101) arms. Of 113 Device assignees, 82 had a device placed, of whom 68 delivered vaginally. Of 101 Control participants, 85 delivered vaginally. At 3 months, 110 participants, 46 Device subjects who received full device treatment, and 64 Controls underwent ultrasound for the per-protocol analysis. No full LAM avulsions (0.0%) occurred in the Device group versus 7 out of 64 (10.9%) in the Control group (p = 0.040; two-tailed Fisher's test). A single maternal serious AE (laceration) was device related; no neonate serious AEs were device related. CONCLUSIONS: The pelvic floor dilator device significantly reduced the incidence of complete LAM avulsion in nulliparous individuals undergoing first vaginal childbirth. The dilator demonstrated an acceptable safety profile and was well received by recipients. Use of the intrapartum electromechanical pelvic floor dilator in laboring nulliparous individuals may reduce the rate of LAM avulsion, an injury associated with serious sequelae including pelvic organ prolapse.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC , defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05172024.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial.

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7-206/7 weeks' gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67-0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58-0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Loss of 3-O-sulfotransferase enzymes, Hs3st3a1 and Hs3st3b1, reduces kidney and glomerular size and disrupts glomerular architecture.

Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan protein cores are modified by sulfotransferases in a highly ordered series of biosynthetic steps resulting in immense structural diversity due to negatively charged sulfate modifications. 3-O-sulfation is the least abundant modification generated by a family of seven isoforms but creates the most highly sulfated HS domains. We analyzed the kidney phenotypes in the Hs3st3a1, Hs3st3b1 and Hs3st6 -knockout (KO) mice, the isoforms enriched in kidney podocytes. Individual KO mice show no overt kidney phenotype, although Hs3st3b1 kidneys were smaller than wildtype (WT). Furthermore, Hs3st3a1-/-; Hs3st3b1-/- double knockout (DKO) kidneys were smaller but also had a reduction in glomerular size relative to wildtype (WT). Mass spectrometry analysis of kidney HS showed reduced 3-O-sulfation in Hs3st3a1-/- and Hs3st3b1-/-, but not in Hs3st6-/- kidneys. Glomerular HS showed reduced HS staining and reduced ligand-and-carbohydrate engagement (LACE) assay, a tool that detects changes in binding of growth factor receptor-ligand complexes to HS. Interestingly, DKO mice have increased levels of blood urea nitrogen, although no differences were detected in urinary levels of albumin, creatinine and nephrin. Finally, transmission electron microscopy showed irregular and thickened GBM and podocyte foot process effacement in the DKO compared to WT. Together, our data suggest that loss of 3-O-HS domains disrupts the kidney glomerular architecture without affecting the glomerular filtration barrier and overall kidney function.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Immunomodulation of salivary gland function due to cancer therapy.

Functional salivary glands (SG) are essential for maintaining oral health, and salivary dysfunction is a persistent major clinical challenge. Several cancer therapies also have off-target effects leading to SG dysfunction. Recent advances highlight the role of SG immune populations in homeostasis, dysfunction and gland regeneration. Here, we review what is known about SG immune populations during development and postnatal homeostasis. We summarize recent findings of immune cell involvement in SG dysfunction following cancer treatments such as irradiation (IR) for head and neck cancers, immune transplant leading to graft-versus-host-disease (GVHD) and immune checkpoint inhibitor (ICI) treatment. The role of immune cells in SG in both homeostasis and disease, is an emerging field of research that may provide important clues to organ dysfunction and lead to novel therapeutic targets.

Valsalva-associated orbital compartment syndrome in the setting of frontoethmoidal mucocele and orbital cellulitis.

Valsalva-associated orbital compartment syndrome in the setting of orbital cellulitis, mucocele, or subperiosteal abscess has not been previously reported. A previously healthy girl presented with orbital cellulitis complicated by a subperiosteal abscess and frontoethmoidal mucocele. On the day of her planned orbitotomy and endoscopic sinus surgery, she developed a Valsalva-associated retrobulbar hemorrhage and elevated intraocular pressure after crying during a blood glucose fingerstick. An urgent canthotomy and cantholysis in addition to the planned endoscopic sinus procedure was performed. She did well post-operatively with normal vision at follow-up. Based on these experiences, there should be a consideration to implement heightened vigilance to prevent or minimize Valsalva maneuvers in orbital cellulitis patients with subperiosteal abscesses or mucoceles extending into the orbit. While it remains unclear whether and to what degree these patients may be at an increased risk of developing retrobulbar hemorrhage leading to orbital compartment syndrome, we hope that this novel report aids in providing another consideration with the goal of preventing vision loss.

Informing the Exposure Landscape: The Fate of Microplastics in a Large Pelagic In-Lake Mesocosm Experiment.

Understanding microplastic exposure and effects is critical to understanding risk. Here, we used large, in-lake closed-bottom mesocosms to investigate exposure and effects on pelagic freshwater ecosystems. This article provides details about the experimental design and results on the transport of microplastics and exposure to pelagic organisms. Our experiment included three polymers of microplastics (PE, PS, and PET) ranging in density and size. Nominal concentrations ranged from 0 to 29,240 microplastics per liter on a log scale. Mesocosms enclosed natural microbial, phytoplankton, and zooplankton communities and yellow perch (Perca flavescens). We quantified and characterized microplastics in the water column and in components of the food web (biofilm on the walls, zooplankton, and fish). The microplastics in the water stratified vertically according to size and density. After 10 weeks, about 1% of the microplastics added were in the water column, 0.4% attached to biofilm on the walls, 0.01% within zooplankton, and 0.0001% in fish. Visual observations suggest the remaining >98% were in a surface slick and on the bottom. Our study suggests organisms that feed at the surface and in the benthos are likely most at risk, and demonstrates the value of measuring exposure and transport to inform experimental designs and achieve target concentrations in different matrices within toxicity tests.

Buccal Versus Vaginal Misoprostol Combined with a Foley Catheter among Individuals with Obesity Undergoing Induction.

BACKGROUND: Combining pharmacologic agents with mechanical ripening achieves the shortest labor duration, yet there is no clear evidence on route of drug administration in obese individuals. The use of buccal misoprostol has shown greater patient acceptance but remains understudied. OBJECTIVE: Our objective was to evaluate the difference in time to delivery of buccal compared with vaginal misoprostol in combination with a Foley catheter (FC) for induction of labor (IOL) in the obese population. STUDY DESIGN: This was a secondary analysis of a randomized controlled trial comparing identical dosages (25 µg) of buccal and vaginal misoprostol in combination with a FC. The parent trial was an institutional review board-approved, randomized clinical trial conducted from June 2019 through January 2020. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2 cm were included. Body mass index (BMI, kg/m2) was stratified. The primary outcome was time to delivery. RESULTS: A total of 215 participants were included. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a body mass index greater than or equal to 30 kg/m2 (vaginal misoprostol-FC: 21.3 hours vs. buccal misoprostol-FC: 25.2 hours, p = 0.006). There was no difference in the cesarean delivery rate between the two groups. Furthermore, patients with a BMI greater than or equal to 30 kg/m2 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for cesarean delivery and adjusting for parity (hazard ratio: 1.2, 95% confidence interval: 1.1-1.7). There were no significant differences in maternal and neonatal outcomes. CONCLUSION: We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI greater than or equal to 30 kg/m2. Vaginal misoprostol should be the preferred route of drug administration for term IOL in this population. KEY POINTS: · Vaginal misoprostol was superior to buccal route among patients with obesity.. · There was no difference in the cesarean delivery rate between the two groups.. · Vaginal misoprostol should be the preferred route of administration among patients with obesity..

Predominantly unilateral laryngomalacia in infants with unilateral vocal fold paralysis.

BACKGROUND: Neonatal unilateral vocal fold paralysis may arise iatrogenically, idiopathically, or in the context of an underlying neurologic disorder. Management is often supportive, focusing on diet modification to allow for safe oral feeding. We describe the clinical course of six infants with unilateral vocal fold paralysis who developed predominantly unilateral laryngomalacia ipsilateral to the affected vocal fold with associated severe respiratory symptoms and feeding difficulty. METHODS: Retrospective review of six infants with unilateral vocal fold paralysis and predominantly unilateral laryngomalacia. Charts were reviewed for etiology of vocal fold paralysis, presenting symptoms, operative details, postoperative course, and outcomes for breathing and swallowing. RESULTS: Etiology of vocal fold paralysis included cardiac surgery in four patients, intubation-related in one, and idiopathic in one. Presenting symptoms included increased work of breathing, stridor, feeding difficulty, respiratory failure requiring noninvasive respiratory support, and weak cry. All infants were on nasogastric tube feedings. Direct microlaryngoscopy with unilateral or predominantly unilateral (conservative contralateral aryepiglottic fold division) supraglottoplasty was performed. Stridor and work of breathing improved in all six patients within 1 week postoperatively. Oral feeding improved in three patients within 2 weeks. Three patients had persistent feeding impairment with improvement within one year. CONCLUSIONS: Predominantly unilateral laryngomalacia may arise in the context of unilateral vocal fold paralysis. Addressing the ipsilateral cuneiform collapse can improve breathing and feeding. This may be an under-described phenomenon and represents an additional reason to include the otolaryngologist early in the care of infants with suspected possible new unilateral vocal fold paralysis. Breathing and swallow can improve post-operatively, but feeding may remain limited by the vocal fold paralysis and any medical comorbidities. Ongoing follow-up and collaboration with speech-language pathology to optimize feeding are important.

Type II Thyroplasty with Bilateral Partial Cricothyroid Myectomy for Vocal Tic in Child with Cerebral Dysgenesis.

Vocal tics can occur in neuropsychiatric disorders and result in familial distress. Management is challenging, particularly in children with developmental delay. A 5-year-old with cerebral dysgenesis presented with a high amplitude, high-frequency vocal tic. Type II thyroplasty with bilateral cricothyroid muscle myectomy was performed after initial botulinum toxin trial. Amount, volume, and pitch of tics significantly decreased, without change in swallow. Benefits persisted at 1-year follow-up. This is the first description of combined type II thyroplasty with cricothyroid myectomy for high-frequency vocal tic. This can be done safely and provide sustained benefit for a rare, impactful voice disorder.

A Multicompartment Assessment of Microplastic Contamination in Semi-remote Boreal Lakes.

Microplastic contamination is ubiquitous across the globe, even in remote locations. Still, the sources and pathways of microplastics to such locations are largely unknown. To investigate microplastic contamination in a semi-remote location, we measured microplastic concentrations in nine oligotrophic lakes within and around the International Institute for Sustainable Development-Experimental Lakes Area in northwestern Ontario, Canada. Our first objective was to establish ambient concentrations of microplastics in bottom sediments, surface water, and atmospheric deposition in semi-remote boreal lakes. Across all lakes, mean shallow and deep sediment microplastic concentrations, near-surface water microplastic concentrations from in situ filtering, and dry atmospheric microplastic deposition rates were 551 ± 354 particles kg-1, 177 ± 103 particles kg-1, 0.2 ± 0.3 particles L-1, and 0.4 ± 0.2 particles m-2 day-1, respectively. Our second objective was to investigate whether microplastic contamination of these lakes is driven by point sources including local runoff and direct anthropogenic inputs or nonpoint sources such as atmospheric deposition. Lakes were selected based on three levels of anthropogenic activity-low, medium, and high-though activity levels were minimal across all study lakes compared with highly populated areas. Whereas a positive correlation would indicate that point sources were a likely pathway, we observed no relationship between the level of anthropogenic activity and microplastic contamination of surface water. Moreover, the composition of microplastics in surface water and atmospheric deposition were similar, comprising mostly polyester and acrylic fibers. Together, these results suggest that atmospheric deposition may be the main pathway of microplastics to these remote boreal lakes. Environ Toxicol Chem 2024;43:999-1011. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Tranexamic acid to reduce blood loss in women at high risk of postpartum hemorrhage undergoing cesarean delivery-a randomized controlled trial.

BACKGROUND: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. Tranexamic acid has proven to be useful in treating hemorrhage from acute blood loss. However, its role in preventing blood loss in women at high risk of postpartum hemorrhage undergoing cesarean delivery is not well studied. OBJECTIVE: This study aimed to assess the role of tranexamic acid in reducing blood loss during elective and unscheduled cesarean deliveries in women at high risk of postpartum hemorrhage. STUDY DESIGN: This was a prospective, placebo-controlled, randomized controlled trial from March 2021 to February 2022 at the Karnatak Lingayat Education Society Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, India. Women at a high risk of postpartum hemorrhage undergoing cesarean delivery were recruited and randomized to receive either tranexamic acid or placebo (1:1) at least 10 minutes before skin incision. High-risk factors for postpartum hemorrhage included obesity, hypertension, multiparity, previous cesarean delivery, multiple pregnancy, abnormally implanted placenta, placenta previa, abruption, uterine leiomyomas, polyhydramnios, and fetal macrosomia. The primary outcome was blood loss, calculated by a formula using pre- and postoperative hematocrit levels. In addition, gravimetrically measured blood loss was measured and compared between the 2 groups. RESULTS: A total of 212 women met the inclusion criteria and were randomized (tranexamic acid [n=106] and placebo [n=106]). The mean blood loss estimates were 400.9 mL in the tranexamic acid group and 597.9 mL in the placebo group (P<.001). The mean gravimetrically measured blood loss estimates were 379.2 mL in the tranexamic acid group and 431.1 mL in the placebo group (P<.001). In addition, there was a significant difference in the fall in hemoglobin levels (1.04 vs 1.61 g/dL) and change in hematocrit levels (3.20% vs 4.95%) from the pre- to postoperative period between the 2 groups (P<.001). No difference in the need for additional uterotonics (P=.26) or the need for postoperative parental iron (P=.18) was noted. No woman was transfused in either group. CONCLUSION: High-risk women receiving tranexamic acid had significantly less blood loss than women receiving placebo during cesarean delivery.

A City-Wide Emissions Inventory of Plastic Pollution.

A global agreement on plastic should have quantitative reduction targets for the emissions of plastic pollution and regular measurements to track success. Here, we present a framework for measuring plastic emissions, akin to greenhouse gas emissions, and demonstrate its utility by calculating a baseline measurement for the City of Toronto in Ontario, Canada. We identify relevant sources of plastic pollution in the city, calculate emissions for each source by multiplying activity data by emission factors for each source, and sum the emissions to obtain the total annual emissions of plastic pollution generated. Using Monte Carlo simulations, we estimate that 3,531 to 3,852 tonnes (T) of plastic pollution were emitted from Toronto in 2020. Littering is the largest source overall (3,099 T), and artificial turf is the largest source of microplastic (237 T). Quantifying source emissions can inform the most effective mitigation strategies to achieve reduction targets. We recommend this framework be scaled up and replicated in cities, states, provinces, and countries around the world to inform global reduction targets and measure progress toward reducing plastic pollution.