Forever Pesticides: A Growing Source of PFAS Contamination in the Environment.

BACKGROUND: Environmental contamination by fluorinated chemicals, in particular chemicals from the per- and polyfluoroalkyl substances (PFAS) class, has raised concerns around the globe because of documented adverse impacts on human health, wildlife, and ecosystem quality. Recent studies have indicated that pesticide products may contain a variety of chemicals that meet the PFAS definition, including the active pesticide ingredients themselves. Given that pesticides are some of the most widely distributed pollutants across the world, the legacy impacts of PFAS addition into pesticide products could be widespread and have wide-ranging implications on agriculture and food and water contamination, as well as the presence of PFAS in rural environments. OBJECTIVES: The purpose of this commentary is to explore different ways that PFAS can be introduced into pesticide products, the extent of PFAS contamination of pesticide products, and the implications this could have for human and environmental health. METHODS: We submitted multiple public records requests to state and federal agencies in the United States and Canada and extracted relevant data from those records. We also compiled data from publicly accessible databases for our analyses. DISCUSSION: We found that the biggest contributor to PFAS in pesticide products was active ingredients and their degradates. Nearly a quarter of all US conventional pesticide active ingredients were organofluorines and 14% were PFAS, and for active ingredients approved in the last 10 y, this had increased to 61% organofluorines and 30% PFAS. Another major contributing source was through PFAS leaching from fluorinated containers into pesticide products. Fluorination of adjuvant products and "inert" ingredients appeared to be limited, although this represents a major knowledge gap. We explored aspects of immunotoxicity, persistence, water contamination, and total fluorine load in the environment and conclude that the recent trend of using fluorinated active ingredients in pesticides may be having effects on chemical toxicity and persistence that are not given adequate oversight in the United States. We recommend a more stringent risk assessment approach for fluorinated pesticides, transparent disclosure of "inert" ingredients on pesticide labels, a complete phase-out of post-mold fluorination of plastic containers, and greater monitoring in the United States. https://doi.org/10.1289/EHP13954.

Pickleball Participation and the Health and Well-Being of Adults-A Scoping Review.

BACKGROUND: Pickleball has grown tremendously in recent years, yet little evidence exists regarding pickleball-related injuries. This scoping review extends current work on pickleball participation by identifying positive and negative health effects associated with the sport. We summarize how pickleball impacts the health and well-being of adult participants. METHODS: Searches were conducted on MEDLINE, CINAHL, ProQuest Nursing, ERIC, SPORTDiscus, PsycINFO, Scopus, CBCA Complete, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses. Selected studies considered aspects of health and/or well-being of adult pickleball participants. Using the population/concept/context framework, participants were healthy, able-bodied adults 18 years of age or over, who had played pickleball at least once. The positive and negative outcomes of pickleball on participants' health and well-being (concept) within the context of pickleball participation were examined. Full-text articles written in English since 2013 were included. Extracted data were tabulated, and a descriptive summary with thematic analysis was completed. RESULTS: This scoping review comprised 27 articles that met the inclusion criteria. Pickleball is promising as an exercise intervention for all adults, and there is evidence of positive social and psychological effects, and health and fitness benefits to participating in pickleball by older adults. CONCLUSIONS: Although we are still in the early stages of studying pickleball, there have been some documented health benefits of using the sport as a physical exercise intervention for adults. More research is needed on the types, prevalence, and severity of pickleball injuries and the sport's impact on younger players.

The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.

Programmed cell death via the both intrinsic and extrinsic pathways is regulated by interactions of the Bcl-2 family protein members that determine whether the cell commits to apoptosis via mitochondrial outer membrane permeabilization (MOMP). Recently the conserved C-terminal sequences (CTSs) that mediate localization of Bcl-2 family proteins to intracellular membranes, have been shown to have additional protein-protein binding functions that contribute to the functions of these proteins in regulating MOMP. Here we review the pivotal role of CTSs in Bcl-2 family interactions including: (1) homotypic interactions between the pro-apoptotic executioner proteins that cause MOMP, (2) heterotypic interactions between pro-apoptotic and anti-apoptotic proteins that prevent MOMP, and (3) heterotypic interactions between the pro-apoptotic executioner proteins and the pro-apoptotic direct activator proteins that promote MOMP.

Baseline single institutional retrospective review of body mass index (BMI) as a prognostic indicator in patients with newly diagnosed glioblastoma (GBM).

PURPOSE: Glioblastoma (GBM) is the most common primary brain cancer in adults with a very poor prognosis. Metabolic drivers of tumorigenesis are highly relevant within the central nervous system, where glucose is the critical source of energy. The impact of obesity on survival outcomes in patients with GBM is not well established. This study investigates the prognostic value of body mass index (BMI) in patients diagnosed with GBM. METHODS: Adult patients with newly diagnosed GBM treated at Thomas Jefferson University Hospital between January 1, 2008, and December 31, 2022, were included in the study. BMI was calculated using the formula BMI = kg/m2. Patients BMI groups were underweight (BMI < 19.00), normal weight (BMI 19.00-24.99), overweight (BMI 25-29.99), and obese (BMI > 30.00). All patients received 60 Gy of radiation therapy with concurrent and adjuvant temozolomide following maximal safe resection. A difference in clinical outcomes of overall survival (OS) and progression-free survival (PFS) were evaluated between the groups using Kaplan-Meier and log-rank tests. RESULTS: A total of 392 patients met inclusion criteria. The median age was 60.3 (range 18.9-86.7), with 144 females and 248 males. Median BMI was 27.0 (Range; 17.7-52.9). Non-overweight GBM patients (BMI < 25.00, OS 2.1 years, CI 1.7-2.4 years) had increased overall survival compared to overweight patients (BMI ≥ 25.00, OS 1.5 years, CI 1.4-1.6 years) (p < 0.001). Patients with MGMT-methylated GBM also had significantly greater OS and PFS compared to MGMT-unmethylated patients (p < 0.001). Non-overweight GBM patients (BMI < 25.00, median PFS 1.5 years, CI 1.3-2.0 years) also had increased progression-free survival compared to overweight patients (BMI ≥ 25.00, median PFS 1.1 years, CI 0.9-1.2 years) (p < 0.001). CONCLUSIONS: Our study indicates normal BMI (19.00-24.99) at the time of GBM diagnosis is a favorable prognostic indicator for overall and progression-free survival. Additional studies are warranted for further analysis of BMI and survival outcomes in GBM patients.

BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains.

The Bcl-2 family controls apoptosis by direct interactions of pro- and anti-apoptotic proteins. The principle mechanism is binding of the BH3 domain of pro-apoptotic proteins to the hydrophobic groove of anti-apoptotic siblings, which is therapeutically exploited by approved BH3-mimetic anti-cancer drugs. Evidence suggests that also the transmembrane domain (TMD) of Bcl-2 proteins can mediate Bcl-2 interactions. We developed a highly-specific split luciferase assay enabling the analysis of TMD interactions of pore-forming apoptosis effectors BAX, BAK, and BOK with anti-apoptotic Bcl-2 proteins in living cells. We confirm homotypic interaction of the BAX-TMD, but also newly identify interaction of the TMD of anti-apoptotic BCL-2 with the TMD of BOK, a peculiar pro-apoptotic Bcl-2 protein. BOK-TMD and BCL-2-TMD interact at the endoplasmic reticulum. Molecular dynamics simulations confirm dynamic BOK-TMD and BCL-2-TMD dimers and stable heterotetramers. Mutation of BCL-2-TMD at predicted key residues abolishes interaction with BOK-TMD. Also, inhibition of BOK-induced apoptosis by BCL-2 depends specifically on their TMDs. Thus, TMDs of Bcl-2 proteins are a relevant interaction interface for apoptosis regulation and provide a novel potential drug target.

Chiroptical Second-Harmonic Tyndall Scattering from Silicon Nanohelices.

Chirality is omnipresent in the living world. As biomimetic nanotechnology and self-assembly advance, they too need chirality. Accordingly, there is a pressing need to develop general methods to characterize chiral building blocks at the nanoscale in liquids such as water─the medium of life. Here, we demonstrate the chiroptical second-harmonic Tyndall scattering effect. The effect was observed in Si nanohelices, an example of a high-refractive-index dielectric nanomaterial. For three wavelengths of illumination, we observe a clear difference in the second-harmonic scattered light that depends on the chirality of the nanohelices and the handedness of circularly polarized light. Importantly, we provide a theoretical analysis that explains the origin of the effect and its direction dependence, resulting from different specific contributions of "electric dipole-magnetic dipole" and "electric dipole-electric quadrupole" coupling tensors. Using numerical simulations, we narrow down the number of such terms to 8 in forward scattering and to a single one in right-angled scattering. For chiral scatterers such as high-refractive-index dielectric nanoparticles, our findings expand the Tyndall scattering regime to nonlinear optics. Moreover, our theory can be broadened and adapted to further classes where such scattering has already been observed or is yet to be observed.

Sterol-like drugs potentiate statin-triggered prostate cancer cell death by inhibiting SREBP2 nuclear translocation.

There is an urgent need to provide immediate and effective options for the treatment of prostate cancer (PCa) to prevent progression to lethal castration-resistant PCa (CRPC). The mevalonate (MVA) pathway is dysregulated in PCa, and statin drugs commonly prescribed for hypercholesterolemia, effectively target this pathway. Statins exhibit anti-PCa activity, however the resulting intracellular depletion of cholesterol triggers a feedback loop that restores MVA pathway activity, thus diminishing statin efficacy and contributing to resistance. To identify drugs that block this feedback response and enhance the pro-apoptotic activity of statins, we performed a high-content image-based screen of a 1508 drug library, enriched for FDA-approved compounds. Two of the validated hits, Galeterone (GAL) and Quinestrol, share the cholesterol-related tetracyclic structure, which is also evident in the FDA-approved CRPC drug Abiraterone (ABI). Molecular modeling revealed that GAL, Quinestrol and ABI not only share structural similarity with 25-hydroxy-cholesterol (25HC) but were also predicted to bind similarly to a known protein-binding site of 25HC. This suggested GAL, Quinestrol and ABI are sterol-mimetics and thereby inhibit the statin-induced feedback response. Cell-based assays demonstrated that these agents inhibit nuclear translocation of sterol-regulatory element binding protein 2 (SREBP2) and the transcription of MVA genes. Sensitivity was independent of androgen status and the Fluva-GAL combination significantly impeded CRPC tumor xenograft growth. By identifying cholesterol-mimetic drugs that inhibit SREBP2 activation upon statin treatment, we provide a potent "one-two punch" against CRPC progression and pave the way for innovative therapeutic strategies to combat additional diseases whose etiology is associated with SREBP2 dysregulation.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

Predictors of recurrence after surgical resection of parafalcine and parasagittal meningiomas.

PURPOSE: Owing to their vicinity near the superior sagittal sinus, parasagittal and parafalcine meningiomas are challenging tumors to surgically resect. In this study, we investigate key factors that portend increased risk of recurrence after surgery. METHODS: This is a retrospective study of patients who underwent resection of parasagittal and parafalcine meningiomas at our institution between 2012 and 2018. Relevant clinical, radiographic, and histopathological variables were selected for analysis as predictors of tumor recurrence. RESULTS: A total of 110 consecutive subjects (mean age: 59.4 ± 15.2 years, 67.3% female) with 74 parasagittal and 36 parafalcine meningiomas (92 WHO grade 1, 18 WHO grade 2/3), are included in the study. A total of 37 patients (33.6%) exhibited recurrence with median follow-up of 42 months (IQR: 10-71). In the overall cohort, parasagittal meningiomas exhibited shorter progression-free survival compared to parafalcine meningiomas (Kaplan-Meier log-rank p = 0.045). On univariate analysis, predictors of recurrence include WHO grade 2/3 vs. grade 1 tumors (p < 0.001), higher Ki-67 indices (p < 0.001), partial (p = 0.04) or complete sinus invasion (p < 0.001), and subtotal resection (p < 0.001). Multivariable Cox regression analysis revealed high-grade meningiomas (HR: 3.62, 95% CI: 1.60-8.22; p = 0.002), complete sinus invasion (HR: 3.00, 95% CI: 1.16-7.79; p = 0.024), and subtotal resection (HR: 3.10, 95% CI: 1.38-6.96; p = 0.006) as independent factors that portend shorter time to recurrence. CONCLUSION: This study identifies several pertinent factors that confer increased risk of recurrence after resection of parasagittal and parafalcine meningiomas, which can be used to devise appropriate surgical strategy to achieve improved patient outcomes.

Stereotactic radiosurgery in the management of non-small cell lung cancer brain metastases: a prospective study using the NeuroPoint Alliance Stereotactic Radiosurgery Registry.

OBJECTIVE: The literature on non-small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS: The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS: Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80-100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3-4 lesions, HR 2.2; 5-14 lesions, HR 2.5). CONCLUSIONS: In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

Targeted immunotherapy for glioblastoma involving whole tumor-derived autologous cells in the upfront setting after craniotomy.

PURPOSE: To date, immunotherapeutic approaches in glioblastoma (GBM) have had limited clinical efficacy as compared to other solid tumors. Here we explore autologous cell treatments that have the potential to circumvent treatment resistance to immunotherapy for GBM. METHODS: We performed literature review and assessed clinical outcomes in phase 1 safety trials as well as phase 2 and 3 autologously-derived vaccines for the treatment of newly-diagnosed GBM. In one recent review of over 3,000 neuro-oncology phase 2 and phase 3 clinical trials, most trials were nonblinded (92%), single group (65%), nonrandomized (51%) and almost half were GBM trials. Only 10% involved a biologic and only 2.2% involved a double-blind randomized trial design. RESULTS: With this comparative literature review we conclude that our autologous cell product is uniquely antigen-inclusive and antigen-agnostic with a promising safety profile as well as unexpected clinical efficacy in our published phase 1b trial. We have since designed a rigorous double-blinded add-on placebo-controlled trial involving our implantable biologic drug device. We conclude that IGV-001 provides a novel immunotherapy platform for historically intransigent ndGBM in this ongoing phase 2b trial (NCT04485949).

Impact of In-house Candida auris Polymerase Chain Reaction Screening on Admission on the Incidence Rates of Surveillance and Blood Cultures With C. auris and Associated Cost Savings.

Background: The impact of strategies for rapid diagnostic screening of Candida auris on hospital operations has not been previously characterized. We describe the implementation of in-house polymerase chain reaction (PCR) testing on admission for screening of colonization with C. auris, associated process improvements, and financial impact. Methods: This study was conducted across an integrated health system. Patients were tested based on risk factors for C. auris carriage. Pre-intervention, the PCR was sent out to a reference laboratory, and postintervention was performed in-house. Changes in the incidence rates (IRs) of C. auris present on admission (CA-POA) and C. auris hospital-onset fungemia (CA-HOF) were assessed using interrupted time series analysis. The economic impact on isolation and testing costs was calculated. Results: Postintervention, the IR of CA-POA doubled (IRR, 2.57; 95% CI, 1.16-5.69; P = .02) compared with the pre-intervention period. The baseline rate of CA-HOF was increasing monthly by 14% (95% CI, 1.05-1.24; P = .002) pre-intervention, while during the postintervention period there was a change in slope with a monthly decrease in IR of 13% (95% CI, 0.80-0.99; P = .02). The median turnaround time (TAT) of the results (interquartile range) was reduced from 11 (8-14) days to 2 (1-3) days. Savings were estimated to be between $772 513.10 and $3 730 480.26. Conclusions: By performing in-house PCR for screening of C. auris colonization on admission, we found a doubling of CA-POA rates, a subsequent decrease in CA-HOF rates, reduced TAT for PCR results, and more efficient use of infection control measures. In-house testing was cost-effective in a setting of relatively high prevalence among individuals with known risk factors.

Chronic inflammatory pulmonary artery lesion causing right pulmonary artery stenosis 15 years post Blalock-Taussig shunt ligation.

Discrete central endovascular pulmonary arterial lesions raise clinical concern for malignancy such as primary pulmonary artery sarcoma. We present a case of a female in her late teens who had an obstructive mid right pulmonary artery lesion found on follow-up imaging 15 years after Tetralogy of Fallot repair. The lesion was in the vicinity of a previously ligated Blalock-Taussig shunt and causing right PA stenosis with delayed perfusion to the right lung, and a flow-related distal left PA aneurysm. The lesion was excised and confirmed histologically to be inflammatory in nature. Intraoperative microbiology demonstrated growth of the Kytococcus species, and she was managed with 6 weeks of intravenous antibiotics, with a full recovery.

CardioCel® for repair of congenital heart defects: nationwide results of over 1000 implants.

OBJECTIVES: To assess the mid-term performance of CardioCel for the repair of congenital heart defects. METHODS: Data were retrospectively collected from databases and hospital records in 3 congenital cardiac surgery centres in Australia. Kaplan-Meier curves and log-rank tests were used to test for associations between patient age, gender, patch type and site of implantation. Multivariable Cox regression was used to test whether any specific implantation site was associated with reintervention risk, after adjusting for age group, gender and patch type. RESULTS: A total of 1184 CardioCel patches were implanted in 752 patients under the age of 18 years. Median age at implant was 12 months [interquartile range (IQR) 3.6-84]. Median follow-up was 2.1 years (IQR 0.6-4.6). Probability of freedom from CardioCel-related reintervention was 93% [95% confidence interval (CI) 91-95] at 1 year, 91% (95% CI 88-93) at 3 years and 88% (95% CI 85-91) at 5 years, respectively. On multivariable regression analysis, aortic valve repair had a higher incidence of reintervention [hazard ratio (HR) = 7.15, P = 0.008] compared to other sites. The probability of reintervention was higher in neonates (HR = 6.71, P = 0.0007), especially when used for augmentation of the pulmonary arteries (HR = 14.38, P = 0.029), as compared to other age groups. CONCLUSIONS: CardioCel can be used for the repair of a variety of congenital heart defects. In our study, in patients receiving a CardioCel implant, reinterventions were higher when CardioCel was used to augment the pulmonary arteries in neonates and for aortic valve repair as compared to other sites.

A Review of Cardiac Surgical Procedures and Their Outcomes for Paediatric Rheumatic Heart Disease in Western Australia.

INTRODUCTION: Surgical intervention is an important treatment modality for advanced rheumatic heart disease (RHD). This study aimed to describe patient characteristics and outcomes from cardiac surgery for RHD in patients referred to the only tertiary paediatric hospital in Western Australia. METHODS: An analysis of patient characteristics and cardiac surgery outcomes in patients with RHD was undertaken, using data from clinical cardiac databases, medical notes, and correspondence from rural outreach clinics. RESULTS: 29 patients (59% female, 97% Aboriginal, Maori or Pacific Islander) underwent 41 valve interventions over 34 cardiac surgeries for RHD between 2000-2018. Median age at first surgery was 12.2 (range 4-16) years. Severe mitral regurgitation (MR) was the most common indication for primary surgery (62%), followed by mixed mitral regurgitation/aortic regurgitation (21%) and severe aortic regurgitation (17%). Mitral valve repair was the most common valve intervention (56%). Two patients had mitral valve replacement (MVR) at first operation, two patients had MVR at second operation and two had MVR at third operation. There was no early mortality. One patient required early (<30 days) reoperation for aortic valve repair failure. Two patients had late reoperations at 3.3 and 6.1 months after the first procedure for MR. Four (14%) patients experienced documented ARF recurrences. Late mortality occurred in 3 (10%) patients, all due to cardiac causes. On last follow-up echocardiogram 5 patients (17%) had moderate MR and none had severe MR. CONCLUSIONS: This is the first study to describe characteristics and outcomes in WA paediatric patients having surgery for RHD. Outcomes are comparable to similar studies, with favourable long-term survival.

Discussion. Has the human population become a sentinel for the adverse effects of PFAS contamination on wildlife health and endangered species?

Global contamination with per- and polyfluoroalkyl substances (PFAS) poses a threat to both human health and the environment, with significant implications for ecological conservation policies. A growing list of peer-reviewed publications indicates that PFAS can harm wildlife health and that the adverse effects associated with PFAS exposure in wildlife are in concordance with human epidemiological studies. The correlation of cross-species data supports a unique perspective that humans can be regarded as a sentinel for PFAS effects in other species. The health harms due to PFAS are potentially most concerning for populations of endangered and threatened species that are simultaneously exposed to PFAS and other toxic pollutants, and also face threats to their survival due to habitat loss, degradation of ecosystems, and over-harvesting. Human epidemiological studies on the PFAS doses associated with health harm present a rich source of information about potential impacts on wildlife health due to PFAS. Our analysis suggests that national and international efforts to restrict the discharges of PFAS into the environment and to clean up PFAS-contaminated sites present an opportunity to protect wildlife from chemical pollution and to advance species conservation worldwide.

Left ventricular remodelling in rheumatic heart disease - trends over time and implications for follow-up in childhood.

BACKGROUND: Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children. METHODS: Children with RHD referred to Perth Children's Hospital (formally Princess Margaret Hospital) (1987-2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes. RESULTS: 146 patients (median age 10 years, IQR 6-14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function. CONCLUSIONS: In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.

Volatile organic compounds emitted by conventional and "green" cleaning products in the U.S. market.

Exposure to cleaning products has been associated with harm to the respiratory system, neurotoxicity, harm to the reproductive system, and elevated risk of cancer, with greatest adverse impacts for workers exposed in an occupational setting. Social and consumer interest in cleaning products that are safer for health created a market category of "green" products defined here as products advertised as healthier, non-toxic, or free from harmful chemicals as well as products with a third-party certification for safety or environmental features. In the present study we examined the air quality impacts of cleaning products and air fresheners, measuring the number, concentrations, and emission factors of volatile organic compounds (VOCs) in an air chamber following product application. Across seven common product categories, 30 products were tested overall including 14 conventional, 9 identified as "green" with fragrance, and 7 identified as "green" and fragrance-free. A total of 530 unique VOCs were quantified with 205 additional VOCs detected below the limits of quantification. Of the quantifiable VOCs, 193 were considered hazardous according to either the California's Department of Toxic Substances Control Candidate Chemicals List or the European Chemical Agency's Classification and Labeling Inventory. The total concentration of VOCs and total emission factors across all products with detections ranged from below limits of detection to 18,708 µg/m3, 38,035 µg/g product and 3803 µg/application. Greater total concentration, total emission factors, and numbers of VOCs were generally observed in conventional cleaning products compared to products identified as "green", particularly compared to fragrance-free products. A hazard index approach was utilized to assess relative risk from measured VOC emissions. The five products with the highest hazard indices were conventional products with emissions of 2-butoxyethanol, isopropanol, toluene and chloroform. Overall, this analysis suggests that the use of "green" cleaning products, especially fragrance-free products, may reduce exposure to VOC emissions.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.