Duration Of Exposure Research Articles

Reduced Freshwater Mussel Juvenile Production as a Result of Agricultural and Urban Contaminant Mixture Exposures.

Freshwater mussels provide invaluable ecological services but are threatened by habitat alteration, poor water quality, invasive species, climate change, and contaminants, including contaminants of emerging concern (CECs). Contaminants of emerging concerns are well documented in aquatic environments, including the Great Lakes Basin, but limited information is available on how environmentally relevant mixtures affect freshwater mussel biology throughout their varied life stages. Our main goal was to assess mussels' reproductive output in response to exposure to agricultural and urban CEC mixtures during glochidial development through juvenile transformation and excystment focusing on how exposure duration and treatment affect: (1) the number of glochidia prematurely released by brooding females, (2) glochidial transformation through host-fish excystment, and (3) the number of fully metamorphosed juveniles able to continue the lifecycle. Mussels and host fish were exposed to either a control water (CW), control ethanol (CE), agriculture CEC mixture (AM), or urban CEC mixture (UM) for 40 and 100 days. We found no effect from treatment or exposure duration on the number of glochidia prematurely released. Fewer partially and fully metamorphosed AM juveniles were observed during the 100-day exposure, compared with the 40-day. During the 40-day exposure, CW produced more fully metamorphosed individuals compared with CE and UM, but during the 100-day exposure AM produced more fully metamorphosed individuals compared with the CW. There was reduction in fully metamorphosed juveniles compared with partially metamorphosed for CE and UM during the 40-day exposure, as well as in the CW during the 100-day exposure. These results will be important for understanding how mussel populations are affected by CEC exposure. The experiments also yielded many insights for laboratory toxicology exposure studies. Environ Toxicol Chem 2024;43:1112-1125. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Exploring the Relationship Among Lipid Profile Changes, Growth, and Reproduction in Folsomia candida Exposed to Teflubenzuron Over Time.

The integration of untargeted lipidomics approaches in ecotoxicology has emerged as a strategy to enhance the comprehensiveness of environmental risk assessment. Although current toxicity tests with soil microarthropods focus on species performance, that is, growth, reproduction, and survival, understanding the mechanisms of toxicity across all levels of biological organization, from molecule to community is essential for informed decision-making. Our study focused on the impacts of sublethal concentrations of the insecticide teflubenzuron on the springtail Folsomia candida. Untargeted lipidomics was applied to link changes in growth, reproduction, and the overall stress response with lipid profile changes over various exposure durations. The accumulation of teflubenzuron in organisms exposed to the highest test concentration (0.035 mg a.s. kg-1 soil dry wt) significantly impacted reproductive output without compromising growth. The results suggested a resource allocation shift from reproduction to size maintenance. This hypothesis was supported by lipid shifts on day 7, at which point reductions in triacylglycerol and diacylglycerol content corresponded with decreased offspring production on day 21. The hypermetabolism of fatty acids and N-acylethanolamines on days 2 and 7 of exposure indicated oxidative stress and inflammation in the animals in response to teflubenzuron bioaccumulation, as measured using high-performance liquid chromatography-tandem mass spectrometry. Overall, the changes in lipid profiles in comparison with phenotypic adverse outcomes highlight the potential of lipid analysis as an early-warning tool for reproductive disturbances caused by pesticides in F. candida. Environ Toxicol Chem 2024;43:1149-1160. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Association between Portal Vein Thrombosis after Umbilical Vein Catheterization and Neonatal Asphyxia

Introduction: Neonatal portal vein thrombosis (PVT) is frequently related to umbilical venous catheterization (UVC), but risk factors remain unclear. This study aims to analyze the variables associated to PVT in near- to full-term newborns with UVC, with a focus on newborns exposed to controlled therapeutic hypothermia (CTH) for hypoxic ischemic encephalopathy (HIE). Methods: This is retrospective cohort study of infants delivered at or after 36 weeks and with a birthweight over 1,500 g. All infants were assessed for UVC location and PVT using ultrasonography performed between day 5 and day 10 after catheterization. Results: Among 213 eligible patients, PVT was diagnosed in 57 (27%); among them, 54 (95%) were localized in the left portal vein branch. With all significant factors in univariate analysis considered, higher gestational age at birth (adjusted OR 1.35; 95% CI: 1.12–1.64, p = 0.002) and duration of UVC placement (adjusted OR 1.36; 95% CI: 1.11–1.67, p = 0.004) were the main risk factors of PVT. Among 87 infants who were cooled for HIE, 31 (36%) had PVT compared to 26 (21%) in infants without CTH. Using a multivariate model including variables linked to treatment procedures only, an increased PVT incidence was statistically associated with UVC duration (adjusted OR 1.33; 95% CI: 1.08; 1.63, p = 0.01) and CTH (adjusted OR 1.94; 95% CI: 1.04–3.65, p = 0.04). Conclusion: Left PVT was frequently observed in near- to full-term neonates with UVC. Among factors linked to treatment procedures, both duration of UVC and CTH exposure for HIE were found to be independent risk factors of PVT.

Effects of Screen Time and Phonemic Segmentation in School Going Children

Background: The rapid proliferation of digital devices has significantly altered children's exposure to screen time, raising questions about its impact on their cognitive and language development. Previous research has indicated both potential benefits and drawbacks of screen time, particularly concerning phonological awareness and language skills in young children. This study seeks to explore the relationship between screen time and phonemic segmentation abilities, a critical component of phonological awareness, in school-going children. Objective: The objective of this study was to investigate the association between the amount of screen time and phonemic segmentation abilities in children aged 4 to 7 years, accounting for variables such as age, gender, and parental education levels. Methods: Conducted at the Department of Speech and Language Pathology, PSRD College of Rehabilitation Sciences, Lahore, this study utilized a cross-sectional design with a sample size of 253 children from various schools. The inclusion criteria were children with normal speech and language development who had exposure to digital devices, excluding those with phonological disorders or developmental delays. The YOPP-Singer Test of Phonemic Segmentation was employed to assess phonemic awareness. Data analysis was performed using SPSS version 25, with ANOVA and Pearson Correlation tests to examine the relationship between screen time and phonemic awareness. Results: Among the participants, 56.1% were in kindergarten, with a gender distribution of 40.3% male and 59.7% female. Parental education varied, with 34.8% holding bachelor's degrees and 24.5% having M.Phil. qualifications. The majority of children (51.8%) reported 1 hour of screen time daily. The ANOVA test revealed no significant difference in phonemic segmentation abilities across different screen time durations (F=.526, p=.665). However, a Pearson Correlation analysis indicated a slight, non-significant positive correlation between screen time and phonemic segmentation abilities (r=.110, p=.080). Conclusion: The study suggests that the amount of screen time, within certain limits, is not significantly associated with phonemic segmentation abilities in children aged 4 to 7 years. These findings highlight the complexity of screen time's impact on language development, suggesting that factors beyond the duration of screen exposure, such as content quality and parental involvement, may play critical roles.

Abstract 5807: Bicycle Toxin Conjugates®for the treatment of solid tumors

Abstract Bicycle Therapeutics is developing a unique class of chemically synthesized medicines. Based on its proprietary bicycle peptide (Bicycle®) phage display platform, Bicycles are a unique class of highly constrained peptides, which have demonstrated utility in the targeted delivery of different classes of payloads (for example cytotoxic agents, radioisotopes, immune modulators) into tumors. Bicycles are currently being explored in the clinic as Bicycle Toxin Conjugates® (BTCs) for targeted delivery of cytotoxic payloads into tumors. BTCs consist of a bicyclic peptide that is conjugated to a cytotoxic payload via a cleavable linker, which allows payload release in the tumor microenvironment or within the tumor cell. BTCs were developed to address the shortcomings of antibody drug conjugates (ADCs) in several ways. First, the small size of BTCs (∼4 kDa) compared to large biologic entities such as monoclonal antibody (mAb)-based conjugates (∼150 kDa) allows rapid distribution to tissues and extensive tumor penetration, which enables rapid delivery of payload into the tumor. Second, the peptidic nature of BTCs results in relatively short, yet tunable, duration of systemic exposure and liver-sparing renal elimination. These properties limit the body’s exposure to payload and should therefore minimize damage to normal tissue. In this body of work, we used in vitro cytotoxicity and cell uptake assays and mouse and rat cell line derived xenograft models for 1) cytotoxicity and anti-tumor activity evaluation, and 2) Bicycle and toxin uptake and biodistribution evaluation. Here, we show that BTCs targeting a number of different tumor antigens can deliver toxins to tumor tissue producing durable responses in a range of preclinical in vivo models, spanning several solid tumor indications. Citation Format: Stephen J. Walsh, Johanna Lahdenranta, Philip Huxley, Gemma Mudd, Gavin Bennett, Amy Brown, Katerine an Rietschoten, Liuhong Chen, Heather Scott, Gabriella Ivanova-Berndt, Katarzyna Dzionek, Mike Rigby, Olga Burenkova, Phil Jeffrey, Paul Beswick, Michael Skynner, Nicholas Keen. Bicycle Toxin Conjugates®for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5807.

Abstract 835: Occupational-related exposure to benzene and risk of female genital cancers: Systematic review and meta-analysis

Abstract Purpose: The IARC monograph has classified benzene as a class I carcinogen, as evidenced by its association with hematological malignancies. However, its association with female genital cancers (ovarian, uterine, cervical) has not been characterized. Therefore, a meta-analysis of cohort studies was performed to determine the possible correlation between occupational benzene exposure and the risk of female genital cancers. Methods: A systematic literature review was conducted that identified 7221 relevant publications. A total of 9 cohort studies detailing occupational exposure to benzene and correlated risk of ovarian, uterine, and cervical cancers were retained, and a meta-analysis (using fixed effects model) was performed. PECOS criteria and STROBE guidelines were followed, and the study protocol was registered in the PROSPERO database (Reg. No. 379720). Study quality was assessed using a modified Newcastle-Ottawa scale (NOS). Results: The summary relative risk (RR) for ever-benzene exposure was 1.22 (95% CI=1.03-1.44, I2<0.001%, n=19); corresponding RR results for female genital cancers incidence and mortality were 1.09 (95% CI=0.92-1.29, I2=5.0%, n=17) and 1.69 (95% CI=1.18-2.4, I2<0.001%, n=9), respectively. These findings were confirmed in sub-analyses by geographical area, industry type, publication year, and levels of benzene exposure. Heterogeneity was detected amongst industries of employment (p-het=0.012) which included petroleum, chemical, printing, and mixed industries categories. Notably, the printing industry (compositors, press operators, and bookbinders) had a summary RR of 2.56 (95% CI=1.45-4.52, I2=35.0%, n=2). However, no heterogeneity was observed for geographical regions (p-het=0.77), duration of benzene exposure (p-het=0.73), publication year (p-het=0.89), or among varying study quality (< or ≥ median NOS score; p-het=0.14). No publication bias was detected (p=0.43). Conclusions: Our meta-analysis identified an association between occupational benzene exposure and the risk of female genital cancers. The association was restricted to the industry of employment. Effects of residual confounding variables cannot be excluded, however, given the present association, there is a potential for causality, especially in workers employed in the printing industry. Citation Format: Darshi Shah, Vincent DeStefano, Veer Shah, Monireh Sadat Seyyedsalehi, Mattia Bonetti, Paolo Boffetta. Occupational-related exposure to benzene and risk of female genital cancers: Systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 835.

Abstract 3333: Targeting the MDM2-p53 interaction: Time- and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index

Abstract Aim We aimed to design an MDM2-p53 antagonist with a differentiated tolerability profile that could be used to treat patients with wild-type TP53 malignancies. As part of an alliance between Newcastle University, Astex Pharmaceuticals, and Cancer Research Horizons, we discovered ASTX295, a potent inhibitor of the MDM2-p53 interaction that is currently under clinical investigation in patients with solid tumors (NCT03975387). We selected ASTX295 as a compound with a predicted short plasma half-life, which we hypothesised would help to mitigate the dose-limiting neutropenia and thrombocytopenia observed with earlier MDM2-p53 antagonists in clinical studies. To examine this hypothesis in vitro, we determined time- and concentration-dependent responses to ASTX295 treatment in healthy volunteer-derived human bone marrow cells, megakaryocytes, and in a panel of human tumor cell lines. Methods Samples containing bone marrow cells from healthy patients undergoing hip surgery were obtained under the ethical approval of the Newcastle Biobank (REC 12/NE/0395). Following Lymphoprep™ separation, cells were treated ex vivo with ASTX295 and seeded for Granulocyte-macrophage (GM) colony-forming assays in methylcellulose. Megakaryocytes were obtained from in vitro differentiation of CD34+ stem/progenitor cells. Human tumor cell lines (including MDM2-amplified SJSA-1) were treated with ASTX295 in vitro and seeded at low density for colony-forming assays. Exposures of 6, 12, or 24h were examined, and the data plotted to calculate LC50 values. Results The clonogenic survival of tumor cells was time-dependent, with LC50 values (mean ± SEM) in SJSA1 cells being 238 ± 46nM and 75 ± 7nM respectively (n = 3-4), following a 12h or 24h exposure to ASTX295. Time-dependent effects were also evident in five human bone marrow samples but with LC50 values of 1.9, >3, >10, >10, and >10uM being achieved at 12h, and 860 ± 268nM at 24h. Megakaryocytes showed similar time-dependent sensitivities in which daily treatment of 2 or 6h over three days did not induce apoptosis while significant cell death was observed when the treatment time was extended to 16-24h daily. In contrast, short, daily pulse treatment of 2-6h in cell lines (MV4-11, MOLM-13, SJSA-1) over three days was sufficient to induce cell death. Conclusions ASTX295 is a potent antagonist of the MDM2-p53 interaction. Collectively, our in vitro data suggest that a shorter exposure to ASTX295 (up to 12h), may help to spare healthy bone marrow cells whilst killing tumor cells. Hence, intermittent exposure to an MDM2-p53 antagonist could favourably modulate its therapeutic index. The predicted short plasma half-life of ASTX295 should provide flexibility in controlling the duration of exposure in vivo, potentially enabling a more bone-marrow sparing approach to MDM2-p53 antagonism to be utilised. Citation Format: Elaine Willmore, Maria Ahn, Suzanne Kyle, Yan Zhao, Huw Thomas, Kenneth S. Rankin, Luke Bevan, Lynsey Fazal, Keisha Hearn, Nicola Wilsher, Justyna Kucia-Tran, Nicola Ferrari, Nicola Wallis, Neil Thompson, John Lyons, Duncan Miller, Celine Cano, Martin E. Noble, Ian R. Hardcastle, Steven Howard, Gianni Chessari, John Lunec, David R. Newell, Steve R. Wedge. Targeting the MDM2-p53 interaction: Time- and concentration-dependent studies in tumor and normal human bone marrow cells reveal strategies for an enhanced therapeutic index [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3333.

A combined toxicological impact on Artemia salina caused by the presence of dust particles, microplastics from cosmetics, and paracetamol

Environmental pollution poses a significant and pressing threat to the overall well-being of aquatic ecosystems in modern society. This study showed that pollutants like dusts from AC filter, fan wings and Traffic dust PM 2.5 were exposed to Artemia salina in pristine form and in combination. The findings indicated that exposure to multi-pollutants had a detrimental effect on the hatching rates of A. salina cysts. Compared to untreated A. salina, the morphology of adult (7th day old) A. salina changed noticeably after each incubation period (24–120 h). Oxidative stress increased considerably as the exposure duration increased from 24 to 120 h compared to the control group. There was a time-dependent decline in antioxidant enzyme activity and total protein concentration. When all particles were used all together, the total protein content in A. salina decreased significantly. All particles showed a considerable decline in survival rate. Those exposed to traffic dust particles showed significantly higher levels of oxidative stress and antioxidant activity than those exposed to other particles.

The Mobile Phone Electromagnetic Radiation Effects on Heart Rate Variability Function

Background: The proliferation of mobile phone usage has given rise to concerns about the potential health effects of electromagnetic fields (EMF), particularly in relation to heart rate variability (HRV), a key indicator of cardiac health. Previous studies have yielded inconsistent results using lower-order statistical measures, leaving a gap in understanding the nonlinear interactions between EMF exposure and HRV. Objective: This study aimed to investigate the effects of mobile phone EMF on HRV by employing bicoherence analysis of ECG data. It sought to determine whether the position of EMF exposure relative to the heart and the duration of exposure affected HRV parameters. Methods: Twenty subjects were recruited for the study, with ECG and EEG data collected under EMF and non-EMF conditions. ECG data were captured using a 12-lead system, with electrodes placed according to standard guidelines. EEG electrodes were positioned following the 10-20 system. Bicoherence and coherence analyses were conducted to assess nonlinear interactions in HRV activity and the relationship between heart and brain signals. The study also considered the duration of EMF exposure, comparing the effects of 10-minute and 40-minute sessions. Results: The bicoherence values for ECG data during EMF exposure at the left ear showed negligible differences, with values ranging between 0.0 to 0.04. However, chest positions V1 and V2 revealed statistically significant larger bicoherence values during non-EMF trials as opposed to EMF trials. Coherence analysis between ECG and EEG demonstrated significantly higher values across the 16-30Hz frequency band during EMF trials. No significant differences were observed for 10-minute EMF exposure, whereas 40-minute exposure sessions indicated a correlation with changes in HRV. Conclusion: The study's findings suggest that mobile phone EMF can affect HRV parameters, with the effects being more pronounced during longer exposure durations and when the source of EMF is closer to the heart. These results support the need for guidelines on safe mobile phone usage and further research into the effects of EMF on cardiac function.

The incidence of upper respiratory infections in children is related to the concentration of vanadium in indoor dust aggregates.

It has been reported that the disease-initiated and disease-mediated effects of aerosol pollutants can be related to concentration, site of deposition, duration of exposure, as well as the specific chemical composition of pollutants. To investigate the microelemental composition of dust aggregates in primary schools of Vilnius and determine trace elements related to acute upper respiratory infections among 6-to 11-year-old children. Microelemental analysis of aerosol pollution was performed using dust samples collected in the classrooms of 11 primary schools in Vilnius from 2016 to 2020. Sites included areas of its natural accumulation behind the radiator heaters and from the surface of high cupboards. The concentrations of heavy metals (Pb, W, Sb, Sn, Zr, Zn, Cu, Ni, Mn, Cr, V, and As) in dust samples were analyzed using a SPECTRO XEPOS spectrometer. The annual incidence rates of respiratory diseases in children of each school were calculated based on data from medical records. The mean annual incidence of physician-diagnosed acute upper respiratory infections (J00-J06 according to ICD-10A) among younger school-age children was between 25.1 and 71.3% per school. A significant correlation was found between vanadium concentration and the number of episodes of acute upper respiratory infections during each study year from 2016 to 2020. The lowest was r = 0.67 (p = 0.024), and the highest was r = 0.82 (p = 0.002). The concentration of vanadium in the samples of dust aggregates varied from 12.7 to 52.1 parts per million (ppm). No significant correlations between the other trace elements and the incidence of upper respiratory infections were found, which could be caused by a small number of study schools and relatively low concentrations of other heavy metals found in the samples of indoor dust aggregates. A significant and replicable correlation was found between the concentration of vanadium in the samples of natural dust aggregates collected in primary schools and the incidence of acute upper respiratory infections in children. Monitoring the concentration of heavy metals in the indoor environment can be an important instrument for the prevention and control of respiratory morbidity in children.

Estimation of the repeatability and reproducibility of test results in determining the degree of cure of protective paint coatings using differential scanning calorimetry

The degree of curing of protective paint-and-varnish coatings for oil country tubular goods is a parameter characterizing the completeness of their polymerization, and allows drawing a conclusion about the final physicomechanical properties and the possibility of using the material under specific conditions. This parameter is considered decisive in conducting acceptance tests and incoming quality control of pipe products with plated protective epoxy coatings despite a low accuracy of the obtained results and the impact of various instrumental factors and methodological approaches. The authors have developed a methodology for determining the curing degree of coatings based on the procedures given in regulatory documents (CSA Z245.20 Series-18, GOST R ISO 21809-2), taking into account the analysis of factors affecting the results of determining the curing degree carried out in the previous work. According to the conducted studies, the rates of heating and cooling during the measurement process, the temperature test program (in particular, the presence and duration of isothermal exposures before heating cycles), and curve processing methods were corrected and selected in the proposed methodology. The aim of this work is the analysis of the precision of the developed method for determining the curing degree of protective coatings to confirm the high accuracy of the obtained values under observing the prescribed procedure. The analysis was carried out by statistical processing of the results obtained in comparative tests performed in four testing laboratories, and included calculation of the repeatability of the results by their standard deviation, reproducibility and assessment of the acceptability of these parameters. The developed procedure for determining the curing degree of protective coatings, from sampling to processing of DSC curves, showed good precision, which indicates the reproducibility and repeatability of the proposed method. The developed method can be used as a unified sequence for determining the curing degree of paints and varnishes used as protective coatings in different laboratories.

Prolonged Hourly Neurologic Examinations are Associated with Increased Delirium and No Discernible Benefit in Mild/Moderate Geriatric Traumatic Brain Injury.

Serial neurologic examinations (NE) are routinely recommended in the ICU within the first 24 hours following a TBI. There are currently no widely accepted guidelines for the frequency of NE. Disruptions to the sleep-wake cycles increase the delirium rate. We aimed to evaluate whether there is a correlation between prolonged Q1-NE and development of delirium and to determine if this practice reduces the likelihood of missing the detection of a process requiring emergent intervention. Retrospective analysis of patients with mild/moderate TBI, admitted to the ICU with serial-NE. Cohorts were stratified by the duration of exposure to Q1-NE, into Prolonged(≥24 h) and Not Prolonged(<24 h). Our primary outcomes of interest was delirium, evaluated using the Confusion Assessment Method (CAM-ICU), radiological progression from baseline images, neurological deterioration (focal neurological deficit, abnormal pupillary exam, or GCS decrease >2), and neurosurgical procedures. A total of 522 patients were included. No significant differences were found in demographics. Patients in the Prolonged Q1-NE group (26.1%) had higher ISS with similar AIS Head, and significantly higher delirium rate [59% vs 35%, p < .001], and a longer Hospital/ICU length of stay when compared to the Not Prolonged Q1-NE group. No neurosurgical interventions were found to be performed emergently as a result of findings on NE. Multivariate analysis demonstrated that Prolonged Q1-NE was the only independent risk factor associated with a 2.5-fold increase in delirium rate. The Number Needed to Harm for prolonged Q1-NE was 4. Geriatric patients with mild/moderate TBI exposed to Q1-NE for periods longer than 24 h had nearly a 3-fold increase in ICU-Delirium rate. One out of five patients exposed to prolonged Q1-NE is harmed by the development of delirium. No patients were found to directly benefit as a result of more frequent neurological examinations.

Experimental evaluation of the impact of ventilation on cooking-generated fine particulate matter in a Chinese apartment kitchen and adjacent room

Cooking is one of the major contributors to indoor pollution. Fine particulate matter (PM2.5) produced during cooking commonly mix into adjacent rooms and elevates indoor PM2.5 concentrations. The risk of human exposure to cooking-generated PM2.5 is mainly related to the exposure duration and particulate matter (PM) concentration. The PM2.5 concentration is influenced by cooking methods and ventilation patterns. Range hoods and open windows are conventional strategies for lowering the concentration of cooking-generated particles. To decrease PM emissions, kitchen air supply systems have been proposed, providing alternative possibilities for kitchen ventilation patterns. The effects of cooking methods, air supply systems, range hoods, and windows on PM2.5 concentrations must be analyzed and compared. To understand and provide advice on reducing exposure to PM2.5 due to cooking activities, we measured the PM2.5 mass concentration in a kitchen and adjacent room during cooking. The identified factors, including cooking method, range hood use, window status, and air supply system, were varied based on orthogonal design. The delay time between the PM2.5 peak in the kitchen and that in the adjacent room was determined. The degree of exposure risk for cooking-generated PM2.5 was evaluated using the mean exposure dose. The results indicated that the mean PM2.5 mass concentration in the kitchen ranged from 22 to 2296 μg/m3. In descending order, the factors affecting the indoor PM2.5 concentration in the apartment studied were range hood use, cooking methods, window status, and air supply system. The PM2.5 peak in the adjacent room occurred 200–800 s later than that in the kitchen. Other conditions being constant in these experiments, the use of range hoods, air supply systems, and windows reduce exposure doses by 90%, 37%, and 51%, respectively. These research results provide insights for reducing human exposure to cooking-generated PM2.5.

Systemic inflammation indices as hematological biomarkers of inflammatory response in non-silicotic workers exposed to respirable silica dust

This cross-sectional study was performed to assess whether systemic inflammatory indices, including systemic inflammation response index (SIRI), systemic immune‑inflammation index (SII), and aggregate index of systemic inflammation (AISI), can be considered as possible inflammatory markers in silica-exposed workers with no diagnosis of silicosis. We studied 371 non-silicotic workers exposed to respirable silica dust (RSD) and 1422 reference workers. The workers’ exposure to RSD were assessed and the inflammatory indices were compared between subgroups of the exposed workers based on the severity and duration of exposure. Correlations between inflammatory indices and the pulmonary function parameters were investigated. Also, the receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off values of the SII, SIRI, and AISI. Significant dose–response relationships were observed between duration of exposure and all indices except monocytes and LMR. No significant interaction was observed between duration of exposure to RSD and smoking. Borderline significant correlations were observed between AISI and SIRI with forced expiratory volume (FEV1) and FEV1 to forced vital capacity (FVC) ratio. Higher AUCs were obtained for SII and AISI, respectively. The cut-off values for these biomarkers to be considered abnormal were > 348.48 for SII, > 183.78 for AISI, and > 0.768 for SIRI. Overall, the present study showed for the first time, that SII, AISI, and SIRI might be considered as available, easy-to-obtain, and non-expensive markers of inflammation in non-silicotic workers with a long duration of exposure to RSD who are at risk of developing silicosis in subsequent years.

Platelet reactivity in young children undergoing congenital heart disease surgery: a NITRIC randomized clinical trial substudy

IntroductionThe international NITRIC trial studied the hypothesis that nitric oxide (NO) applied into the cardiopulmonary bypass (CPB) oxygenator in infants would improve recovery after heart surgery. In a substudy, we evaluated the effect of NO applied into the CPB oxygenator on the (re)activity of platelets measured as fibrinogen binding (platelet aggregation) and P-selectin expression (platelet degranulation) in young children.MethodsPlatelet activity (without agonist exposure) and reactivity (after stimulation by an agonist) was studied in a single center substudy of the NITRIC trial, a multicenter, randomized trial that studied administration of 20 parts per million (ppm) NO during CPB in children younger than 2 years. Blood was collected at 4 time points (T1- T4); before CPB, after CPB start, before and after weaning. Flow cytometry-based platelet activity and reactivity in the presence of 5 agonists was tested. Differences on P-selectin expression and fibrinogen binding (median fluorescence intensity (MFI)) were analyzed with mixed effect modelling (MEM).ResultsBlood samples were obtained in 22 patients allocated to NO and 20 controls. Platelet counts dropped after T1 due to the hemodilution of blood in all patients (p < 0.001). Beta coefficients for NO allocation derived from the MEM models on fibrinogen binding and P-selectin expression were small (standardized beta coefficients on fibrinogen binding were 0.07[0.03, 0.11] and on P-selectin expression 0.05[0.03, 0.08]) and non-significant. CPB duration did not affect platelet reactivity (standardized beta coefficients 0.09[0.02, 0.12] with p > 0.27) in any of the MEMs.Conclusion20 ppm NO administration in the sweep gas of the CPB oxygenator did not affect platelet reactivity in young children undergoing heart surgery. Interestingly, duration of CPB exposure also did not have an effect on platelet (re)activity.Trial registrationANZCTR, ACTRN12617000821392. Registered 5 June 2017, https://anzctr.org.au/

Tailoring the structural, morphological, surface wettability and hardness features of Makrofol HS for surface applications: effect of DBD treatment

ABSTRACT In current research, Makrofol HS polymeric films have been utilized to evaluate the alterations in the surface properties under an atmospheric-pressure dielectric barrier discharge (DBD) plasma source. Upon DBD plasma exposure with various exposure durations ranging from 10 min to 120 min, the structural, surface wettability, surface free energy, surface roughness, and hardness features of Makrofol HS films have been studied and analyzed using different techniques. The FTIR spectra demonstrated that small changes in the band intensities correspond to the C-O-C as well as C=O bonds. Further, the changes in the absorption bands are correlated to the treatment time, leading to two critical processes, degradation, and crosslinking. The results of surface wettability displayed that the liquids' contact angle decreased from 84 ± 3o, 77 ± 3o and 62 ± 2o for water, glycerol, and dimethyl to 45 ± 1o, 42 ± 1o, and 36 ± 1o for untreated and treated samples at the highest treatment time, respectively. Also, the surface free energy significantly amended with increasing plasma exposure time. This modification in the treated surface indicates the increase in the polar groups on the treated surfaces, which then become hydrophilic surfaces. The samples' surface roughness parameters Ra, Rq, and Rz increased from 0.057 ± 0.003, 0.084 ± 0.004 and 0.366 ± 0.02 mm for untreated samples to 1.463 ± 0.073, 1.707 ± 0.085, and 6.839 ± 0.34 mm for treated samples at the highest treatment time, respectively. The Vickers hardness measurements showed an increase in the Vickers hardness from 12.31 ± 0.61 kgf/mm2 for the untreated sample to 44.89 ± 2.24 kgf/mm2 for the treated sample at the highest duration.

Self-Explaining Roads: Effects of road design on speed choice

One of the leading principles for road design is the notion of Self-Explaining Roads(SER). According to this notion, the design and layout of the road environment should automatically elicit behavior that is appropriate for that type of road. The current study investigated the effects of the road environment (i.e., the presence of particular road elements such as the presence/absence of edge lines, and a physical separation between driving lanes) on driving speed choice in the Netherlands for roads in- and outside the city limits (ICL and OCL). A total of 462 participants (all car drivers) were exposed to either 152 ICL or 152 OCL pictures of road environments for either a short (300 ms in Experiment 1, 200 ms in Experiment 2) or long duration (1500 ms) and indicated as fast as possible which speed they would drive given the road environment they viewed. All images were labeled with respect to the presence or absence of particular road elements. A linear mixed model was used to determine the effects of road elements on speed choice and response time. The results showed that the presence of certain road elements impacted the speed chosen. For example, inside the city limits, relative to no bicycle lane, a bicycle lane painted on the road reduced driving speed while a separate bike lane increased the speed chosen. Also, central line markings (relative to no line marking) and a road made of asphalt (relative to pavers) were associated with higher speeds. Outside city limits, having multiple lanes (versus one lane) was related to higher speeds and having two driving directions without separation (versus a one-way road) was related to lower speed choices. Importantly, exposure duration (200 /300 ms versus 1500 ms) only had a marginal effect, indicating that road users generally only need a brief glimpse of the road to be able to decide what speed to drive. Consistent with the principles of SER, we conclude that categorization and the associated speed decision is fast, operating within a single glance and is impacted by the road elements present in the environment. Finally, we believe our method constitutes a valuable tool in road design, as it allows one to efficiently and effectively gauge the impact of various road elements in large population samples.

Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.

Integrated Safety Analysis of Abrocitinib in 635 Adolescent Patients With Moderate-To-Severe Atopic Dermatitis With Over 1000 Patient-Years of Exposure

Introduction: Abrocitinib, an oral, once-daily, Janus kinase 1–selective inhibitor, was efficacious and well tolerated in adolescent patients with moderate-to-severe atopic dermatitis (AD) exposed for approximately 1 year of treatment. Here, we describe the updated long-term integrated safety profile of abrocitinib in adolescent patients in the JADE clinical program.Methods: A total of 635 adolescent patients (12 to &lt;18 years; exposure: 1011.4 patient-years [PY]) were pooled for safety analysis from the phase 3 JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676), and REGIMEN (NCT03627767) and subsequently enrolled in the ongoing phase 3 extension trial JADE EXTEND (NCT03422822; data cutoff: September 25, 2021). Incidence rates (IRs; number of unique patients with events/100 PY) of severe adverse events (SAEs) and AEs of special interest were assessed.Results: Of the total 635 adolescents, 490 received the same abrocitinib dose throughout exposure (730.6 PY); 289 received abrocitinib 200 mg (424.5 PY) and 201 received abrocitinib 100 mg (306.1 PY). Duration of exposure was ≥96 weeks in 38% and 37%, and ≥144 weeks in 8% and 4% of patients who received abrocitinib 200 mg or 100 mg, respectively. In the 200-mg and 100-mg arms, AEs occurred in 243 (84%) and 153 (76%) patients; 8% (IR [95% CI], 5.87 [3.76-8.74]) and 9% (5.87 [3.48-9.27]) experienced SAEs, and 10% (6.96 [4.69-9.93]) and 8% (5.13 [2.93-8.33]) discontinued the study due to AEs, respectively. IRs of AEs of special interest were 1.84 (95% CI, 0.79-3.62) and 1.28 (0.35-3.27) for serious infection, 2.11 (0.97-4.01) and 1.62 (0.53-3.77) for all herpes zoster (HZ) infections, and 0.69 (0.14-2.03) and 0.32 (0.01-1.77) for opportunistic HZ infections in the 200-mg and 100-mg arms, respectively. One patient (aged 16 years) in the 200-mg arm had a nonfatal venous thromboembolism event (pulmonary embolism; IR, 0.23 [95% CI, 0.01-1.28]); patient had a family history of pulmonary embolism. There were no events of nonmelanoma skin cancer or other malignancies, tuberculosis, or other opportunistic infections (excluding HZ), major adverse cardiovascular events, or deaths.Conclusions: In this integrated safety analysis using the September 2021 data cut from the ongoing JADE EXTEND trial, abrocitinib had an acceptable long-term safety profile in adolescents with moderate-to-severe AD.

Navigation versus fluoroscopy in minimalinvasive iliosacral screw placement

IntroductionWhen needed operative treatment of sacral fractures is mostly performed with percutaneous iliosacral screw fixation. The advantage of navigation in insertion of pedicle screws already could be shown by former investigations. The aim of this investigation was now to analyze which influence iliosacral screw placement guided by navigation has on duration of surgery, radiation exposure and accuracy of screw placement compared to the technique guided by fluoroscopy.Methods68 Consecutive patients with sacral fractures who have been treated by iliosacral screws were inclouded. Overall, 85 screws have been implanted in these patients. Beside of demographic data the duration of surgery, duration of radiation, dose of radiation and accuracy of screw placement were analyzed.ResultsWhen iliosacral screw placement was guided by navigation instead of fluoroscopy the dose of radiation per inserted screw (155.0 cGy*cm2 vs. 469.4 cGy*cm2p < 0.0001) as well as the duration of radiation use (84.8 s vs. 147.5 s p < 0.0001) were significantly lower. The use of navigation lead to a significant reduction of duration of surgery (39.0 min vs. 60.1 min p < 0.01). The placement of the screws showed a significantly higher accuracy when performed by navigation (0 misplaced screws vs 6 misplaced screws—p < 0.0001).ConclusionBased on these results minimal invasive iliosacral screw placement guided by navigation seems to be a safe procedure, which leads to a reduced exposure to radiation for the patient and the surgeon, a reduced duration of surgery as well as a higher accuracy of screw placement.