Endocrine Disruptors in Pregnancy: Effects on Mothers and Fetuses-A Review.

Background/Objectives: Endocrine disruptors are ubiquitous agents in the environment and are present in everyday consumer products. These agents can interfere with the endocrine system, and subsequently the reproductive system, especially in pregnancy. An increasing number of studies have been conducted to discover and describe the health effects of these agents on humans, including pregnant women, their fetuses, and the placenta. This review discusses prenatal exposure to various endocrine disruptors, focusing on bisphenols, phthalates, organophosphates, and perfluoroalkyl substances, and their effects on pregnancy and fetal development. Methods: We reviewed the literature via the PubMed and EBSCO databases and included the most relevant studies. Results: Our findings revealed that several negative health outcomes were linked to endocrine disruptors. However, despite the seriousness of this topic and the abundance of research on these agents, it remains challenging to draw strong conclusions about their effects from the available studies. This does not allow for strong, universal guidelines and might result in poor patient counseling and heterogeneous approaches to regulating endocrine disruptors. Conclusions: The seriousness of this matter calls for urgent efforts, and more studies are needed in this realm, to protect pregnant patients, and ultimately, in the long term, society.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. METHODS: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. RESULTS: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. CONCLUSIONS: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk.

Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are man-made chemicals that are extensively used in industrial and consumer products worldwide and in aqueous film-forming foam utilized in firefighting. As such, our exposure to PFAS is essentially ubiquitous. Given the long half-lives of these degradation-resistant chemicals, virtually, all people are carrying a body burden of PFAS. Health concerns related to PFAS are growing such that the National Academies of Sciences, Engineering and Medicine has recommended standards for clinical follow-up of individuals with high PFAS blood levels, including prioritizing screening for dyslipidemia. The link between PFAS and dyslipidemia has been extensively investigated, and evidence for associations is compelling. However, dyslipidemia is not the only cardiovascular risk factor with which PFAS is associated. Here, we review the epidemiological evidence for links between PFAS of concern identified by the National Academies of Sciences, Engineering and Medicine and risk factors for cardiovascular disease, including overweight/obesity, glucose intolerance, hypertension, dyslipidemia, and hyperuricemia. Moreover, we review the potential connections of PFAS with vascular disease and atherosclerosis. While observational data support associations between the National Academies of Sciences, Engineering and Medicine PFAS and selected cardiac risk factors, additional research is needed to establish causation and better understand how exposure to PFAS leads to the development of these conditions.

Uptake and distribution of perfluoroalkyl substances by grafted tomato plants cultivated in a contaminated site in northern Italy.

Poly- and perfluoroalkyl substances (PFAS) are highly persistent and mobile pollutants raising alarming concerns due to their capability to accumulate in living organisms and exert toxic effects on human health. We studied the accumulation of different PFAS in the leaves and fruits of tomato plants grown on a PFAS-polluted soil in North-East Italy. Tomato plants were grafted with different rootstocks characterized by different vigor, and irrigated with PFAS-polluted groundwater. Leaves and fruits of the first and sixth truss were analyzed at full plant maturity. All tomato varieties accumulated PFAS in leaves and fruits, with the highest concentrations detected in the most vigorous rootstock and reflecting the PFAS concentration profile of the irrigation water. PFAS with a chain length from 4 to 8 C atoms and with carboxylic and sulfonic functional groups were detected in plant leaves, whereas only carboxylic C4, C5, and C6 PFAS were detected in tomato fruits. A general trend of decreasing PFAS concentrations in fruits upon increasing height of the plant trusses was observed. Calculation of the target hazard quotient (THQ) showed increasing values depending on the plant vigor. The hazard index (HI) values showed values slightly higher than 1 for the most vigorous plants, indicating potential risks to human health associated with the consumption of contaminated tomato fruits.

Influence of the dilution method on the intraocular duration of C3F8 in vitrectomy for macular hole: a randomized clinical trial

ABSTRACT Purpose: To compare the injection of small amounts of undiluted C3F8 with the traditional gas injection in vitrectomy for macular hole treatment. Methods: This clinical trial included 26 individuals divided into two groups. Group 1 received an intravitreal injection of 0.9-1.0 mL of 100% C3F8, and Group 2 received 15-20 mL of 20% C3F8. Results: The median intraocular gas duration was 31 days in Group 1 and 34 in Group 2. The median letter gains in corrected distance visual acuity for the 26th postoperative week were 20 letters in Group 1 and 12.5 in Group 2. The median intraocular pressure was normal in both groups. Primary anatomical success was 11/13 in both groups. Conclusions: The use of C3F8 gas in a small undiluted volume is an alternative that slightly reduces the duration of the gas without negatively affecting the anatomical and visual response.

Analysis of the Maximum Efficiency and the Maximum Net Power as Objective Functions for Organic Rankine Cycles Optimization.

Maximum efficiency and maximum net power output are some of the most important goals to reach the optimal conditions of organic Rankine cycles. This work compares two objective functions, the maximum efficiency function, ß, and the maximum net power output function, ω. The van der Waals and PC-SAFT equations of state are used to calculate the qualitative and quantitative behavior, respectively. The analysis is performed for a set of eight working fluids, considering hydrocarbons and fourth-generation refrigerants. The results show that the two objective functions and the maximum entropy point are excellent references for describing the optimal organic Rankine cycle conditions. These references enable attaining a zone where the optimal operating conditions of an organic Rankine cycle can be found for any working fluid. This zone corresponds to a temperature range determined by the boiler outlet temperature obtained by the maximum efficiency function, maximum net power output function, and maximum entropy point. This zone is named the optimal temperature range of the boiler in this work.

Semifluorinated Alkanes as New Drug Carriers-An Overview of Potential Medical and Clinical Applications.

Fluorinated compounds have been used in clinical and biomedical applications for years. The newer class of semifluorinated alkanes (SFAs) has very interesting physicochemical properties including high gas solubility (e.g., for oxygen) and low surface tensions, such as the well-known perfluorocarbons (PFC). Due to their high propensity to assemble to interfaces, they can be used to formulate a variety of multiphase colloidal systems, including direct and reverse fluorocarbon emulsions, microbubbles and nanoemulsions, gels, dispersions, suspensions and aerosols. In addition, SFAs can dissolve lipophilic drugs and thus be used as new drug carriers or in new formulations. In vitreoretinal surgery and as eye drops, SFAs have become part of daily clinical practice. This review provides brief background information on the fluorinated compounds used in medicine and discusses the physicochemical properties and biocompatibility of SFAs. The clinically established use in vitreoretinal surgery and new developments in drug delivery as eye drops are described. The potential clinical applications for oxygen transport by SFAs as pure fluids into the lungs or as intravenous applications of SFA emulsions are presented. Finally, aspects of drug delivery with SFAs as topical, oral, intravenous (systemic) and pulmonary applications as well as protein delivery are covered. This manuscript provides an overview of the (potential) medical applications of semifluorinated alkanes. The databases of PubMed and Medline were searched until January 2023.

Systematic review and meta-analysis of epidemiologic data on vaccine response in relation to exposure to five principal perfluoroalkyl substances.

BACKGROUND: Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear. OBJECTIVE: The goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in loge antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA). DATA SOURCE: We conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies conducted in humans, including mother-child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data. RESULTS: The 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in loge[antibody concentration] per doubling of serum PFAS) with 95% confidence intervals that excluded zero ("statistical support"), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, -0.06 (-0.10, -0.01; moderate) and in children, -0.10 (-0.16, -0.03; moderate); for Diphtheria in children, -0.12 (-0.23, -0.00; high); for Rubella in all ages, -0.09 (-0.17, -0.01; moderate), and for Tetanus in children, -0.12 (-0.24, -0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, -0.06 (-0.11, -0.01; moderate) and in children, -0.10 (-0.18, -0.03; moderate); for Rubella in all ages, -0.09 (-0.15, -0.03; high) and in children, -0.12 (-0.20, -0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, -0.03 (-0.06, -0.00; moderate) and in children, -0.05 (-0.09, -0.00; low); and for Rubella in children, -0.07 (-0.11, -0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations. LIMITATIONS AND CONCLUSIONS: Epidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias.

Gas tamponade followed by laser treatment for macular retinal detachment secondary to optic pit / Tamponamento com gás seguido de laser para descolamento de retina secundário à fosseta de disco óptico

ABSTRACT Purpose: The study aimed to describe anatomic and visual outcomes associated with perfluoropropane intravitreal injection followed by laser treatment for macular retinal detachment secondary to optic disc pit. Methods: A single-center, retrospective study. Medical records of all patients treated at a tertiary retina referral center were evaluated between 2011 and 2018 for congenital optic disc pit-associated macular detachment with 0.3 ml 100% perfluoropropane intravitreal injection followed by retinal laser photocoagulation along the temporal optic disc margin as the initial treatment. Results: Six patients with optic disc pit-associated macular detachment were identified, with postoperative follow-up ranging from 13 to 52 months (mean: 28 months). Spectral domain optical coherence tomography (SD-OCT) showed complete fluid resolution without recurrence in five of the six cases. Four cases showed complete reabsorption after Intravitreal perfluoropropane plus laser, one patient needed an extra procedure (pars plana vitrectomy with inner limiting membrane peeling and pedicle flap inversion over the temporal optic disc margin) to achieve complete fluid reabsorption, and one patient had persistent intraretinal fluid and denied additional surgeries. The time between the initial procedure and total fluid reabsorption varied from 6.5 to 41 months (mean: 19.5 months). Best-corrected visual acuity improved after surgery on the last follow-up visit in all cases. Conclusion: 100% perfluoropropane intravitreal injection followed by photocoagulation along temporal optic disc margin was associated with anatomic and visual improvement in most cases, representing an alternative treatment approach for optic disc pit-associated macular detachment.

RESUMO Objetivo: Descrever os resultados anatômicos e visuais associados à injeção intravítrea de perfluoropropano seguida de tratamento a laser para descolamento de retina macular secundário à fosseta do disco óptico. Métodos: Estudo retrospectivo em um único centro. Foram revisados os prontuários médicos dos pacientes com descolamento macular associado a fosseta do disco óptico congênito em um centro de referência terciário de retina entre 2011 e 2018. Todos receberam como estratégia de tratamento inicial injeção intravítrea de perfluoropropano 100% seguido por fotocoagulação a laser ao longo da margem temporal do disco óptico. Resultados: Foram identificados seis pacientes com descolamento macular associado a fosseta do disco óptico durante o período do estudo. O seguimento pós-operatório variou de 13 a 52 meses, com média de 28 meses. SD-OCT demonstrou resolução completa do fluido em cindo dos seis casos, sem recorrência. Quatro casos apresentaram reabsorção completa após perfluoropropano intravítreo associado a laser, e um paciente necessitou de procedimento adicional (vitrectomia via pars plana com peeling da membrana limitante interna e inversão do retalho do pedículo sobre a margem temporal do disco óptico) para obter reabsorção completa de fluidos. Um paciente apresentou fluido intrarretiniano persistente e negou tratamentos adicionais. O tempo entre o procedimento inicial e a resolução completa do fluido variou entre 6,5 a 41 meses, com média de 19,5 meses. A acuidade visual corrigida melhorou após a cirurgia, considerando a última consulta de acompanhamento em todos os casos. Conclusão: A injeção intravítrea de perfluoropropano 100% seguida de fotocoagulação ao longo da margem temporal da margem do disco óptico foi associada à melhora anatômica e visual na maioria dos casos e representa uma abordagem terapêutica alternativa para o descolamento macular associado a fosseta do disco óptico.

Enhancing Dual-State Emission in Maleimide Fluorophores through Fluorocarbon Functionalisation.

Herein, a library of trifluoroethyl substituted aminomaleimide derivatives are reported with small size and enhanced emissions in both solution and solid-state. A diCH2 CF3 substituted aminochloromaleimide exhibits the most efficient dual-state emission (Φf >50 % in solution and solid-state), with reduced quenching from protic solvents. This is attributed to the reduction of electron density on the maleimide ring and suppressed π-π stacking in the solid-state. This mechanism was explored in-depth by crystallographic analysis, and modelling of the electronic distribution of HOMO-LUMO isosurfaces and NCI plots. Hence, these dual-state dyes overcome the limitations of single-state luminescence and will serve as an important step forward for this rapidly developing nascent field.

Official health communications are failing PFAS-contaminated communities.

BACKGROUND: Environmental health agencies are critical sources of information for communities affected by chemical contamination. Impacted residents and their healthcare providers often turn to federal and state agency webpages, fact sheets, and other documents to weigh exposure risks and interventions. MAIN BODY: This commentary briefly reviews scientific evidence concerning per- and polyfluoroalkyl substances (PFAS) for health outcomes that concern members of affected communities and that have compelling or substantial yet differing degree of scientific evidence. It then features official documents in their own language to illustrate communication gaps, as well as divergence from scientific evidence and from best health communication practice. We found official health communications mostly do not distinguish between the needs of heavily contaminated communities characterized by high body burdens and the larger population with ubiquitous but substantially smaller exposures. Most health communications do not distinguish levels of evidence for health outcomes and overemphasize uncertainty, dismissing legitimate reasons for concern in affected communities. Critically, few emphasize helpful approaches to interventions. We also provide examples that can be templates for improvement. CONCLUSIONS: Immediate action should be undertaken to review and improve official health communications intended to inform the public and health providers about the risks of PFAS exposure and guide community and medical decisions.

Long-Chain PFASs-Free Omniphobic Membranes for Sustained Membrane Distillation.

Omniphobic membranes possessing high wetting resistance have been created for the treatment of challenging hypersaline feedwaters with low surface tension through membrane distillation (MD). However, virtually all such membranes are fabricated with long-chain per- and polyfluoroalkyl substances (PFASs, ≥8 fluorinated carbons). The environmental risks and high bioaccumulation potential of long-chain PFASs have raised increasing concerns. Developing highly wetting-resistant MD membranes while avoiding the use of long-chain PFASs is essential to improve the viability of MD for resilient and sustainable water purification. We demonstrate that MD membranes with exceptional wetting resistance can be designed through the combination of hierarchically structured membranes consisting of re-entrant texture at different length scales and (ultra)short-chain fluorocarbons, which have lower acute toxicity and bioaccumulation potentials than long-chain PFASs. Our hierarchically structured membrane with three-tier micro/nanostructure fabricated with short-chain fluorocarbon possesses superior wetting resistance, which is comparable to or higher than the long-chain PFASs-based omniphobic membranes reported in the literature. Furthermore, the hierarchically structured membranes fabricated with ultrashort-chain fluorocarbons display improved wetting resistance against feedwaters with low surface tension. Our findings indicate that long-chain PFASs are not required when designing wetting-resistant membranes and that the balance between sustainability and wetting resistance should be tailored to the wetting potential of the feedwater.

Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry.

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (Kd) for each compound were calculated using regression analysis of the dose-dependent changes in HSA melting temperature. Estimated Kd values for HSA binding of octanoic acid, decanoic acid, hexadecenoic acid, ibuprofen, and warfarin agreed with established values. The binding affinities for 24 PFAS that included perfluoroalkyl carboxylic acids (C4-C12), perfluoroalkyl sulfonic acids (C4-C8), mono- and polyether perfluoroalkyl ether acids, and polyfluoroalkyl fluorotelomer substances were determined. These results demonstrate the utility of this differential scanning fluorimetry assay as a rapid high-throughput approach for determining the relative protein-binding properties and identification of chemical structures involved in binding for large numbers of structurally diverse PFAS.

Characterization and Tribological Performances of Graphene and Fluorinated Graphene Particles in PAO.

Graphene has been widely used as a lubricating additive to reduce the energy consumption of engines and improve fuel economy because of its unique crystal structure. Herein, graphene (GR) and fluorinated graphene (F-GR) nanoparticles were prepared by ball milling and liquid-phase exfoliation. The SEM/EDS, HRTEM, XPS, Raman spectrometer, X-ray spectrometer, FTIR were used to investigate the morphologies, surface groups, and crystal structure of two kinds of graphene materials. The influence of loads on the tribological properties of two kinds of particles was investigated in Poly Alpha Olefin (PAO6) using a UMT-2 reciprocating tribometer. Results showed that the crystal structure of GR is better than F-GR. F-GR can improve the lubrication performance of PAO6. For PAO6 containing 1 wt% F-GR at 10 N, the average friction coefficient and average wear rate decreased by 12.3% and 87% relative to pure PAO6, respectively. However, the high load resulted in an inconspicuous anti-wear and anti-friction effect. The influence of F-GR on the tribological behavior of PAO6 was more substantial than that of GR. The friction and wear mechanisms attributed to F-GR quickly entered the interface between the friction pairs. Friction-induced F-GR nanosheets mainly took the tribo-chemical reactions to participate in the lubrication film formation and helped achieve a low friction coefficient and wear rate.

Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms.

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.

1,1,1,2,3,4,4,5,5,5-Decafluoropentane (HFC-4310mee).

HFC-43-10mee is a volatile liquid at room temperature and used as a cleaning agent, aerosol, etc. HFC-43-10mee has low acute inhalation toxicity; 4-hour LC50 in rats of approximately 11,000 ppm. The compound was not a skin or eye irritant and was not a skin sensitizer. A cardiac sensitization response was not observed at 5000 ppm. Inhalation exposure resulted in neurotoxicity consisting of tremors, convulsions, jerking, ataxia, abnormal gait, etc. at exposure concentrations of 2000 ppm and above. Within approximately 30 min of exposure the clinical signs appeared and resolved within 1-2 h during exposure; the rats appeared to adapt such that these clinical signs were no longer observed. The neurotoxicity observed was considered an acute response to HFC-43-10mee. In a 90-day study, rats exposed to 2000 ppm resulted in sporadic clinical signs of neurotoxicity. At 3500 ppm, the clinical signs were evident on most exposure days although as the study progressed the apparent incidence declined likely reflecting adaptation. The NOAEL was 500 ppm. Based on the occurrence of the clinical signs in this and other studies, an acute threshold for neurotoxicity was evident at approximately 2000 ppm and above. No developmental or reproductive toxicity were evident at 2000 ppm, although clinical signs of neurotoxicity occurred in maternal or parental rats at 2000 ppm. No effects on offspring were observed. HFC-43-10mee was not genotoxic in vitro or in vivo. Based on the data, the 8-h TWA WEEL value is 225 ppm (2320 mg/m3). The 15-min STEL is 700 ppm (7217 mg/m3).

A clinically acceptable strategy for sensitizing anti-PD-1 treatment by hypoxia relief.

The hypoxic tumor microenvironment (TME) hinders the effectiveness of immunotherapy. Alleviating tumor hypoxia to improve the efficacy of immune checkpoint inhibitors (ICIs) represented by programmed cell death protein 1 (PD-1) antibody has become a meaningful strategy. In this study, we adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition. Both in vivo and in vitro experiments showed that liposomes modified with perfluorocarbon or hemoglobin (PFC@lipo or Hb@lipo) were able to efficiently load and release oxygen, relieving tumor hypoxia. However, the gas release behavior of PFC@lipo was uncontrollable, which might induce acute hyperoxia side effects during intravenous injection and reduce its biosafety. In contrast, whether administered locally or systemically, Hb@lipo revealed high animal tolerance, and was much safer than commercial HIF-1α inhibitor (PX-478), displaying prospects as a promising oxygen carrier for clinical practice. Pharmacodynamic experiments suggested that Hb@lipo helped PD-1 antibody break the therapeutic bottleneck and significantly inhibited the progression of 4 T1 breast cancer. But in CT26 colon cancer, the combination therapy failed to suppress tumor growth. After in-depth analysis and comparison, we found that the ratio of M1/M2 tumor associated macrophages (TAMs) between these two tumor models were dramatically different. And the lower M1/M2 ratio in CT26 tumors limited the anti-tumor effect of combination therapy. In this study, three methods for alleviating tumor hypoxia were compared from the perspectives of biosafety, efficacy and clinical applicability. Among them, Hb@lipo stood out, and its combined use with PD-1 antibody exhibit a distinct synergistic suppression effect on tumors with more M1 macrophages presented in the microenvironment. Our work provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxia.

Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome.

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients' outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

Comparison of Perfluorodecalin and Silicone Oil as Initial Tamponade for Giant Retinal Tear-Associated Retinal Detachment.

INTRODUCTION: To compare visual outcomes and complication rates of giant retinal tear-associated retinal detachment (GRT-RD) cases treated with short-term perfluorodecalin (PFD) tamponade versus silicone oil (SiO). METHODS: Database analysis of patients with GRT-RD operated on in the period from 1 January 2014 to 31 December 2019. RESULTS: Forty-five patients were operated for GRT-RD using PFD or SiO during this period. Two children, 7 patients receiving gas tamponade, and 2 lost to follow-up were excluded. Eighteen eyes (40%) received PFD and 27 (60%) received SiO. There were 15/18 (83%) macula-sparing cases in the PFD group and 18/27 (67%) in the SiO group (p = 0.13). The mean duration of oil tamponade was 91 days for SiO and 7.6 days for PFD (p < 0.0001). The mean length of follow-up was 274.5 days for PFD and 668.9 days for SiO. The mean BCVA was 6/18 (63.4 ± 26.0 ETDRS letters) for SiO and 6/12 (72.9 ± 12.7 ETDRS letters) for PFD (p = 0.42). Analysing macula-sparing pseudophakic eyes, the BCVA was 6/12 (67.4 ± 25.9 letters, n = 18) for SiO eyes and 6/9 (76.8 ± 9.9 letters, n = 11) for PFD eyes (p = 0.54). The recurrence rate was 22% (6/27) for SiO and 6% (1/18) for PFD (p = 0.12). The rate of cystoid macular oedema (CMO) was 22% for SiO and 22% for PFD. Epiretinal membrane (ERM) was found in 26% of SiO cases and 22% of PFD cases. Loss of vision after oil removal was not observed. Seven eyes (26%) receiving SiO and none receiving PFD developed chronic ocular hypertension (OHT) (p = 0.02). CONCLUSIONS: Short-term tamponade with PFD for GRT-RD appears similar to tamponade with SiO in terms of the visual outcomes and complication rates.

The concentration of several perfluoroalkyl acids in serum appears to be reduced by dietary fiber.

Fiber-rich food intake has been associated with lower serum concentrations of perfluoroalkyl substances (PFAS) in some studies and dietary fiber was related to lower serum PFAS in a recent study. Given the previous epidemiologic data suggesting that fiber might decrease serum PFAS concentrations, we examined the relation of serum PFAS concentrations to intake of dietary fiber in National Health and Nutrition Examination Survey (NHANES) data. We examined the PFAS-fiber association among 6482 adults who participated in the NHANES, 2005-2016. Fiber intake was estimated based on two 24-hour diet recalls. We adjusted the models for determinants of PFAS and potentially confounding factors such as intake of foods reported to increase PFAS exposure. Results were expressed as the percent difference in PFAS concentration per interquartile range (IQR) increase in fiber (and 95 percent confidence interval), and the NHANES sampling parameters were used to make the results generalizable to the U.S. The adjusted percent difference in perfluorooctanoic acid (PFOA) per IQR increase in fiber was -3.64 (-6.15, -1.07); for perfluorooctane sulfonic acid (PFOS) was -6.69 (-9.57, -3.73), and for perfluorononanoic acid (PFNA) was -8.36 (-11.33, -5.29). These results suggest that dietary fiber increases the gastrointestinal excretion of PFOA, PFOS, and PFNA. Because fiber also lowers serum cholesterol, in some studies of the serum cholesterol-PFAS relationship confounding by fiber may be worth evaluating.