High Exposure Group Research Articles

Radiation exposure in pediatric patients with early onset scoliosis: A longitudinal single-center study

BackgroundThere is no consensus regarding the acceptable level of medical radiation exposure in patients with early-onset scoliosis. This study aimed to quantify radiation exposure in these patients and investigate factors associated with high exposure. MethodsPatients with early-onset scoliosis who received care for their spine deformity and other comorbidities in our institution were retrospectively reviewed. Cumulative radiation exposure and total number of imaging studies were recorded. Patients with ≥30 mSv exposure were classified as high exposure and analyzed to clarify factors associated with high exposure. ResultsThirty-five patients were included for analysis. The etiology of scoliosis was idiopathic in 8 patients, congenital in 7, syndromic in 8, and neuromuscular in 12. Fifteen patients underwent 19 spinal surgeries. The types of operation performed were definitive fusion (n = 12), vertebrectomy for hemivertebra (n = 2), growing rod (n = 1), lengthening (n = 3), and revision/partial implant removal (n = 1). The mean cumulative radiation dose was 22.3 mSv (range, 2.5–94.5 mSv). Spine radiography and computed tomography combined accounted for 15.0 mSv (range, 2.4–52.5 mSv, 67.3% of the mean cumulative dose). The mean radiation dose was significantly higher in patients who underwent spinal surgery than in those who did not (31.2 mSv vs. 15.6 mSv). The high-exposure group comprised 10 patients (1 idiopathic, 1 congenital, 5 syndromic, and 3 neuromuscular scoliosis) and 8 underwent 11 spinal operations. Among 8 patients who underwent spinal surgery, the cumulative radiation dose for spine was ≥30 mSv and spine computed tomography was performed an average of 4.0 times. ConclusionsNearly one-third of patients with early-onset scoliosis and half of patients who underwent spinal surgery had >30 mSv radiation exposure due to multiple computed tomography. Medical radiation exposure and associated cancer risk should be considered when treating these patients.

Toxic Effects of Methylene Blue on the Growth, Reproduction and Physiology of Daphnia magna.

Methylene blue (MB) is a disinfectant used in aquaculture to prevent and treat fish diseases. However, the release of MB can pose a risk to the receiving water bodies. Zooplankton are the most sensitive organisms among aquatic life. Hence, this study examined the acute and chronic toxic effects of MB on zooplankton using Daphnia magna (D. magna) as a test organism to provide basic data for risk assessment. The results show that 48 h-EC50 and 24 h-LC50 were 61.5 ± 2.3 and 149.0 ± 2.2 μg/L, respectively. Chronic exposure to MB affected the heart rate, beat frequency of the thoracic limbs, and reproductive ability of D. magna at environmental concentrations higher than 4.7 μg/L. The cumulative molts, time to production of the first brood, and total number of living offspring were affected at different MB concentrations, while "abortions" were observed in high-exposure groups. The activity of superoxide dismutase was increased, while glutathione S-transferase activity was stimulated at low concentrations and inhibited at high concentrations. In addition, the malondialdehyde content increased with increasing concentrations of MB. Our findings demonstrate the impact of MB on the reproduction and growth of freshwater species, as well as their physiological responses. These results have implications for establishing guidelines on the use of MB in aquaculture and setting discharge standards.

P-045 Effects of seminal BPA levels on human sperm parameters and gene expression

Abstract Study question Are high BPA levels in human seminal fluid associated with low sperm metrics and changes in gene expression? Summary answer A trend towards an inverse relationship between seminal BPA and sperm count was observed. Expression of androgen receptor mRNA was down-regulated with high BPA exposure. What is known already Bisphenol A (BPA) is a widespread industrial chemical, used as the key monomer of polycarbonate plastics and epoxy resins. While some countries have introduced bans/stringent regulation for BPA, it continues to be widely used especially in North America, where its use is only limited in baby products. BPA has been detected in human seminal fluid and has been correlated with decreased sperm counts and motility - crucial factors in determining male fertility, which continue to decrease. We have demonstrated that in vitro BPA exposure can reduce motility, mitochondrial membrane potential, and capacitation in mature bovine spermatozoa. Study design, size, duration In collaboration with CCRM, Toronto, seminal fluid samples were collected from 90 patients undergoing fertility assessment between 2021 and 2023. Typical evaluations such as sperm counts, motility, and morphology were recorded by the clinic (following WHO guidelines). Samples were then shipped to the University of Guelph for further investigations. Information on outcomes for patients who underwent subsequent IVF cycles like fertilization rates and pregnancy rates were also recorded at the clinic. Participants/materials, setting, methods At the University of Guelph, seminal BPA levels were measured through an enzyme-linked immunosorbent assay (ELISA; My BioSource), then compared to sperm metrics obtained by the clinic. Next, a GeNorm analysis was performed to determine the most stable reference genes for subsequent qPCR analysis. The relative mRNA expression of three key genes related to male reproduction (androgen receptor (AR), cyp17a1 and cyp11a1) were quantified and compared between groups with high and low BPA content. Main results and the role of chance BPA concentrations in the seminal fluid samples ranged between 0-3000 pg/mL, with most samples containing 35-1000 pg/mL. When samples were graphed according to increasing BPA levels, no relationships were observed between BPA and motility or morphology rates. However, a negative trend between BPA and sperm count was detected, although this was not significant. Samples were then divided into high- (total 15 samples with >700 pg/mL) and low- (total 15 samples with <100 pg/mL) BPA content groups. The GeNorm M value indicated that HPRT1 and HMBS were the most stable reference genes across the groups. qPCR analysis on three biological replicates in technical triplicates showed that androgen receptor mRNA expression was significantly higher in sperm exposed to low seminal BPA compared to the high BPA exposure group (p = 0.03913). This finding is particularly interesting as AR expression has previously been positively correlated with sperm count, motility and morphology. cyp17a and cyp11a mRNA expression was undetectable in human spermatozoa under our experimental conditions. Future steps include increasing the sample size to increase the power of the correlation studies between sperm quality parameters and ART success rates. Furthermore, other fertility-related genes will be investigated at both the mRNA (qPCR) and protein levels (flow cytometry). Limitations, reasons for caution Relatively small sample size; duration of study must be extended to gain information on outcomes of ART cycles; many samples in the mid-range of BPA are excluded from gene expression studies. Wider implications of the findings These results can ultimately display a relationship between BPA exposure and male fertility and provide further insights into the molecular mechanisms through which BPA exerts its effects. Ultimately, this research can drive changes to guidelines/exposure limits for BPA, especially in North America. Trial registration number not applicable

Development of a Dynamic Network Model to Identify Temporal Patterns of Structural Malformations in Zebrafish Embryos Exposed to a Model Toxicant, Tris(4-chlorophenyl)methanol.

Embryogenesis is a well-coordinated process relying on precise cues and environmental signals that direct spatiotemporal embryonic patterning. Quite often, when one error in this process occurs, others tend to co-occur. We posit that investigating the co-occurrence of these abnormalities over time would yield additional information about the mode of toxicity for chemicals. Here, we use the environmental contaminant tris(4-chlorophenyl)methanol (TCPMOH) as a model toxicant to assess the relationship between exposures and co-occurrence of developmental abnormalities in zebrafish embryos. We propose a dynamic network modeling approach to study the co-occurrence of abnormalities, including pericardial edema, yolk sac edema, cranial malformation, spinal deformity, delayed/failed swim bladder inflation, and mortality induced by TCPMOH exposure. TCPMOH-exposed samples revealed increased abnormality co-occurrence when compared to controls. The abnormalities were represented as nodes in the dynamic network model. Abnormalities with high co-occurrence over time were identified using network centrality scores. We found that the temporal patterns of abnormality co-occurrence varied between exposure groups. In particular, the high TCPMOH exposure group experienced abnormality co-occurrence earlier than the low exposure group. The network model also revealed that pericardial and yolk sac edema are the most common critical nodes among all TCPMOH exposure levels, preceding further abnormalities. Overall, this study introduces a dynamic network model as a tool for assessing developmental toxicology, integrating structural and temporal features with a concentration response.

Transmissibility of mpox to the general population from travellers returning to South Korea.

Based on data from three imported mpox cases in South Korea, the overall attack rate was determined to be 1%, while a secondary attack rate of 14% was estimated in the high-exposure group.

Assessment of Diagnostic Accuracy and Clinical Utility of DNA Methylation (5-mC) in Detecting Severity of Occupational Lead Exposure.

This study investigated the diagnostic accuracy (DA) and clinical utility (CU) of DNA methylation (5 methylcytosine) in occupational Pb-exposure from Pb based industry. Blood Lead levels (BLLs) were measured using the ICP-OES method. The total DNA methylation (5-mC) was quantified using ELISA method. Based on their BLLs, the Pb-exposed workers were categorised into three groups: low (< 10µg/dL), moderate (10-30µg/dL), and high exposure (> 30µg/dL). DNA methylation (5-mC) was significantly lower in moderate and high Pb-exposure groups when compared to the low Pb-exposure group. Workers exposed to high levels of Pb-exposure, the DA variables of 5-mC showed that the sensitivity was 74.7% [95% CI 65.4-84.0], specificity was 69.6% [95% CI 50.8-88.4], positive predictive value (PPV) was 89.9% [95% CI 82.7-97.0], Postive likelihood ratio (LR+) was 2.454 [95% CI 1.3-4.6], and diagnostic odds ratio (DOR) is 6.3 [95% CI 6.5-7.7]. In moderate Pb-exposure, the DA variables of 5-mC revealed that the sensitivity is 64.9% [95% CI 55.2-74.5], the specificity is 69.6% [95% CI 50.8-88.4], the PPV is 89.7% [95% CI 82.5-97.0], the LR+ is 2.132 [95% CI 1.13-4.03], and the DOR is 4.2 [95% CI 3.6-5.7]. The high Pb-exposure group had higher DA metrics when compared to moderate Pb exposure. The clinical utility (CU+) of 5-mC was found to have good utility of 0.671 [95% CI 0.566-0.776] in the high Pb exposure group and fair utility of 0.582 [95% CI 0.470-0.694] in moderate Pb exposure group. In conclusion, DNA methylation (5mC) could be used as a predictive biomarker for high Pb-exposure.

Exposure-response analysis of alemtuzumab in pediatric allogeneic HSCT for nonmalignant diseases: the ARTIC study

AbstractAlemtuzumab (anti-CD52 antibody) is frequently prescribed to children with nonmalignant diseases undergoing allogeneic hematopoietic stem cell transplantation (HSCT) to prevent graft failure (GF) and acute graft-versus-host disease (aGVHD). The aim of this multicenter study was the characterization of alemtuzumab population pharmacokinetics to perform a novel model–based exposure-response analysis in 53 children with nonmalignant immunological or hematological disease and a median age of 4.4 years (interquartile range [IQR], 0.8-8.7). The median cumulative alemtuzumab dose was 0.6 mg/kg (IQR, 0.6-1) administered over 2 to 7 days. A 2-compartment population pharmacokinetics model with parallel linear and nonlinear elimination including allometrically scaled bodyweight (median, 17.50 kg; IQR, 8.76-33.00) and lymphocyte count at baseline (mean, 2.24 × 109/L; standard deviation ± 1.87) as significant pharmacokinetic predictors was developed using nonlinear mixed effects modeling. Based on the model–estimated median concentration at day of HSCT (0.77 μg/mL; IQR, 0.33-1.82), patients were grouped into a low- (≤0.77 μg/mL) or high- (>0.77 μg/mL) exposure groups. High alemtuzumab exposure at day of HSCT correlated with delayed CD4+ and CD8+ T-cell reconstitution (P value < .0001) and increased risk of GF (P value = .043). In contrast, alemtuzumab exposure did not significantly influence the incidence of aGVHD grade ≥2, mortality, chimerism at 1 year, viral reactivations, and autoimmunity at a median follow-up of 3.3 years (IQR, 2.5-8.0). In conclusion, this novel population pharmacokinetics model is suitable for individualized intravenous precision dosing to predict alemtuzumab exposure in pediatric allogeneic HSCT for nonmalignant diseases, aiming at the achievement of early T-cell reconstitution and prevention of GF in future prospective studies.

Dietary polystyrene nanoplastics exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in Monopterus albus

Microplastics and nanoplastics (MPs and NPs) are abundant, persistent, and widespread environmental pollutants that are of increasing concern as they pose a serious threat to ecosystems and aquatic species. Identifying the ecological effects of NPs pollution requires understanding the effects of changing nanoplastics concentrations in aquatic organisms. Monopterus albus were orally fed three different concentrations of 100 nm polystyrene nanoplastics (PS-NPs): 0.05 %, 0.5 %, and 1 % of the feed for 28 days. Nanoplastics significantly activated the PPAR signaling pathway, Acyl-CoA oxidase 1 (ACOX1), carnitine palmitoyltransferase 1a (CPT1A), angiopoietin-like 4 (ANGPTL4), and phosphoenolpyruvate carboxykinase (PCK) at the mRNA level, resulting in disturbed lipid metabolism. Glutathione peroxidase (GSH-px) activity, catalase (CAT) activity, and malondialdehyde (MDA) were significantly elevated in the high nanoplastics-feeding exposure group, leading to oxidative stress in the liver. Overexpression of the cytokines genes Interleukin 1 (IL1B) and Interleukin-8 (IL8), Tumor necrosis factor alpha (TNF-α), activation of MAPK signaling pathway, and increased gene expression of c-Jun amino-terminal kinases (JNK) and p38 indicate that exposure to NPs may lead to hepatopancreas apoptosis through oxidative stress and inflammation. In summary, dietary PS-NPs exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in M. albus. The results of this study provide valuable ecotoxicological data for a better understanding of the biological fate and effects of nanoplastics in M. albus.

Sex-specific differences in the circulatory response to postural stress among young adults with adverse childhood experiences (ACEs)

Adverse childhood experiences (ACEs)—a highly prevalent assortment of traumatic childhood events (e.g., abuse)—are strongly linked to adult cardiovascular disease (CVD), though differently among males and females. Biological sex differences in the circulatory response to physiological stress (e.g., postural stress) have been well-characterized; however, whether ACEs affect this response differently among males and females remains unclear. This study tested the hypothesis that ACEs affect the circulatory response to head-up tilt (HUT; postural stress) differently among males and females. Three hundred ( n = 156 female; 22.4 ± 1.8 years) young adults recruited through the Niagara Longitudinal Heart Study (NLHS) were included in the current analyses. ACEs were assessed (Childhood Trust Events Survey 2.0) and participants were dichotomized into high (≥4 ACEs) and low (&lt;4 ACEs) exposure groups. Beat-by-beat mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were recorded during 10-minutes of supine rest and 5-minutes of 60° HUT. Sex-stratified, mixed-model regression analyses assessed the effect of ACEs on changes (Δ) in MAP and HR from supine rest to HUT, adjusting for age, body mass index, physical activity, and smoking status. During HUT, MAP increased to a similar extent in males with high and low ACEs exposure (ΔMAP: 11.5 ± 10.8 mmHg vs. 10.1 ± 10.9 mmHg, respectively; p &gt; 0.05). In contrast, MAP increased to a greater extent in females with high ACEs exposure compared to females with low ACEs exposure (ΔMAP: 11.3 ± 10.4 mmHg vs. 5.9 ± 9.8 mmHg, respectively; p = 0.003). HR increased during HUT in males with both high and low ACEs exposure; however, it increased to a lesser extent in males with high ACEs exposure compared to males with low ACEs exposure (ΔHR: 14.7 ± 7.5 bpm vs. 18.7 ± 8.1 bpm, respectively; p = 0.015). In females, HR increased to a similar extent during HUT in those with high and low ACEs exposure (ΔHR: 16.5 ± 8.1 bpm vs. 17.6 ± 8.9 bpm, respectively; p &gt; 0.05). These data suggest that ACEs affect the circulatory response to postural stress differently in males and females. Further, these data imply that sex-specific differences in circulatory regulation can be observed as early as young adulthood in those reporting high ACEs exposure. This work was supported by the Canadian Institute of Health Research (CIHR) and Brock University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Quantitative analysis of the minimum days of dietary survey to estimate dietary pesticide exposure: Implications for dietary pesticide sampling strategy

Populations are exposed to pesticides through diet on a daily basis. However, there is no research guiding how to evaluate dietary pesticide exposure, and researchers used 1-day, 3-days, 7-days or even longer dietary survey to evaluate without any consensus. It is important for dietary pesticide evaluation to identify the minimum survey days. To increase knowledge of this, a data combination was applied between a two-wave consecutive repeated-measures study in Baoding City and the Fifth China Total Diet Study. Further policy consistency on pesticides were evaluated to explain its credibility. We computed the sensitivity and specificity to evaluate how well different days of dietary survey classify participants with high exposure, and calculated the minimum days required to estimate the participant-specific mean at different acceptable error range. With 1 day of dietary survey, the classification sensitivity was low (<0.6) for total HCH, endosulfan, chlordane, cyhalothrin, allethrin, and prallethrin; that for the other pesticides was high sensitivity (≥0.6). Sensitivity increased as the number of days increased, and the maximum marginal sensitivity increase (≥0.039) occurred from 1 to 2 days for all pesticides except phenothrin, whose maximum marginal sensitivity increase (0.042) occurred from 2 to 3 days. The specificity increased gradually from 0.8 to 0.9 from 1 to 7 days. Under the acceptable error range of 0.5%, 3–28 days were required for participant-specific mean estimation and 1–7 days were required when acceptable error range was shrunk in 1%. Only 1 day was enough if 5% error range was acceptable. In conclusion, 3 days in the study period was cost-effective to distinguish high exposure group, and it rose to 7 when estimating participant-specific mean from a conservative perspective. This study can serve as a reference to determine the minimum survey days for epidemiological studies employing dietary surveys.

Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos.

Difenoconazole is a type of triazole fungicide that is widely used in the treatment of plant diseases. Triazole fungicides have been shown in several studies to impair the development of the nervous system in zebrafish embryos. There is still little known about difenoconazole-induced neurotoxicity in fish. In this study, zebrafish embryos were exposed to 0.25, 0.5, and 1 mg/L of difenoconazole solution until 120 h post-fertilization (hpf). The difenoconazole-exposed groups showed concentration-dependent inhibitory tendencies in heart rate and body length. Malformation rate and spontaneous movement of zebrafish embryos increased, and the locomotor activity decreased in the highest exposure group. The content of dopamine and acetylcholine was reduced significantly in difenoconazole treatment groups. The activity of acetylcholinesterase (AChE) was also increased after treatment with difenoconazole. Furthermore, the expression of genes involved in neurodevelopment was remarkably altered, which corresponded with the alterations of neurotransmitter content and AChE activity. These results indicated that difenoconazole might affect the development of the nervous system through influencing neurotransmitter levels, enzyme activity, and the expression of neural-related genes, ultimately leading to abnormal locomotor activity in the early stages of zebrafish.

Comparison of developmental toxicity of benzophenone-3 and its metabolite benzophenone-8 in zebrafish

Benzophenone-3 (BP-3) as one of frequently used organic UV filters has been considered an emerging pollutant due to its toxicities. Benzophenone-8 (BP-8) is one of the main metabolites of BP-3 in organisms. Current reports show that BP-8 may be more toxic than BP-3. However, difference of their toxicities on embryonic development has rarely been reported. In this study, zebrafish embryos were chosen as the target organism to explore the developmental toxicities of BP-3 and BP-8. Non-targeted metabolomic analysis was performed to compare their modes of action. Results showed that BP-8 exposures led to higher bioaccumulation and lower hatching rate of zebrafish larvae than BP-3. Both BP-8 and BP-3 exposures caused behavioral abnormalities of zebrafish larvae, but no significant difference was found between them. At the metabolome level, 1 μg/L BP-3 and 1 μg/L BP-8 exposures altered neuroactive ligand-receptor interaction pathway and FoxO signaling pathway, respectively, which might be involved in the abnormal behaviors in zebrafish larvae. For higher exposure groups (30 and 300 μg/L), both BP-3 and BP-8 exposures changed metabolism of cofactors and vitamins of zebrafish larvae. Exposure of BP-3 altered the metabolism by pantothenate and CoA biosynthesis pathway, while BP-8 exposure changed riboflavin metabolism and folate biosynthesis. The above results indicated different modes of action of BP-3 and BP-8 in zebrafish embryonic development. This study sheds new light to biological hazards of BP-3 due to its metabolism in aquatic organisms.

Relationship between systemic inflammation and lung injury induced by chromate exposure: A cross–sectional study in workers

Hexavalent chromium [Cr(VI)] compounds, known as “Group I Human Carcinogen” and “Category I Respiratory Sensitizer”, posed great challenges to the respiratory system. A cross–sectional study was undertaken among chromate workers. Serum club cell protein 16 (CC16) and soluble urokinase–type plasminogen activator receptor (suPAR) were measured using ELISA. Thirteen macrophage–related mediators were tested using cytometric bead array. After controlling for sex, age, smoking status, drinking status and BMI, each increase of one–unit of Ln–transformed blood Cr was related to the increase of IL–1beta [Beta (95% CI), 7.22(1.14, 13.29)%, P = 0.021], IL–23 [8.5(1.15, 15.85)%, P = 0.021], IFN–gamma [3.14(0.15, 6.13)%, P = 0.040], and suPAR [9.31(2.5, 16.12) %, P = 0.008], as well as the increase of CC16 by 3.88(0.42, 7.34) % (P = 0.029). Moreover, these inflammatory mediators played an mediation role in the rise of CC16 caused by Cr(VI). The exposure–response curve analysis revealed a substantial nonlinear association of IFN–gamma and suPAR with CC16, thus the mediation effect of INF–gamma and suPAR required cautious interpretation. The positive connection between macrophage–related mediators was stronger in the high exposure group than in the low exposure group, suggesting that high concentration of chromate might promote a complex interplay within the immune system.

Outdoor particulate matter exposure affects metabolome in chronic obstructive pulmonary disease: Preliminary study.

The metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers. Thirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation. Metabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively. PM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD.

Interpersonal transmission of ROCD symptoms and susceptibility to infidelity in romantic relationships

Relationship obsessive–compulsive disorder (ROCD) is a disabling presentation of obsessive-compulsive disorder (OCD) centering on close interpersonal relationships. Previous studies focused on the personal consequences of ROCD symptoms. Yet, studies investigating the consequences of ROCD symptoms on one's partner are scarce. In this study, we assessed whether exposure to romantic partners' elevated ROCD symptoms would heighten participants' ROCD symptoms and would increase participants' evaluation of their own and their partners' susceptibility to infidelity. Heterosexual couples (Ncouples = 50; Mage = 25.8) completed self-report questionnaires. One randomly selected partner of each romantic dyad was then randomly allocated to being exposed to information suggesting their partner has low (low-exposure) or high (high-exposure) levels of ROCD symptoms. Results indicated that participants in the high-exposure group showed higher ROCD symptoms than participants in the low-exposure group. Exposure to allegedly elevated levels of partners' ROCD symptoms also led participants to evaluate their own and their partners' susceptibility to infidelity as higher than participants in the low-exposure group, particularly among participants with pre-existing ROCD symptoms. These results illustrate a ‘contagious’ effect of unmediated exposure to partners' ROCD symptoms and its potentially unfavorable consequences. Clinical implications regarding partner involvement in the treatment of ROCD are discussed.

Association of drug burden index with delirium in community-dwelling older adults with dementia: a longitudinal observational study.

The Drug Burden Index (DBI) is a validated tool for assessing the dose-dependent cumulative exposure to sedative and anticholinergic medications. However, the increased risk of delirium superimposed dementia (DSD) with high DBI levels has not yet been investigated. This study aimed to examine the potential association between DBI scores and delirium in community-dwelling older adults with dementia. A total of 1105 participants with cognitive impairment underwent a comprehensive geriatric assessment. Experienced geriatricians made the final diagnosis of delirium based on DSM-IV-TR and DSM-V. We calculated the DBI as the sum of all sedatives and anticholinergics taken continuously for at least four weeks before admission. Polypharmacy was defined as regular use of five or more medications. We classified the participants as having no exposure (DBI = 0), low exposure (0 < DBI < 1), and high exposure (DBI ≥ 1). Of the 721 patients with dementia, the mean age was 78.3 ± 6.7years, and the majority were female (64.4%). In the whole sample, low and high exposures to anticholinergic and sedative medications at admission were 34.1% (n = 246) and 38.1% (n = 275), respectively. Patients in the high-exposure group had higher physical impairment (p = 0.01), higher polypharmacy (p = 0.01), and higher DBI scores (p = 0.01). In the multivariate Cox regression analysis, high exposure to anticholinergic and sedative medications increased the risk of delirium 4.09-fold compared to the no exposure group (HR = 4.09, CI: 1.63-10.27, p = 0.01). High exposure to drugs with sedative and anticholinergic properties was common in community-dwelling older adults. A high DBI was associated with DSD, highlighting the need for an optimal prescription in this vulnerable population. The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT04973709 Registered on 22 July 2021.

Measuring adverse childhood experiences with latent class trajectories

BackgroundAdverse childhood experiences (ACEs) are associated with several negative health and behavioral outcomes during adolescence, but most of the extant research has employed ACEs scores at one or two time points. Studies have not assessed whether latent class ACEs trajectories affect adolescent problem behaviors and conditions. ObjectivesWe used longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS, n = 3444) to assess ACEs at several time points and empirically developed latent class trajectories. We then examined the sociodemographic characteristics of youth who belonged to each trajectory group. We next evaluated whether the ACEs trajectories during childhood were associated with delinquent behavior, substance use, and symptoms of anxiety or depression. Finally, we explored whether closeness to mother buffered the impact of ACEs on these outcomes. MethodsEight types of ACEs were captured in the FFCWS data. ACE scores were assessed at year one, three, five, and nine, along with the outcomes during year 15. Trajectories were estimated with a semiparametric latent class models. ResultsThe analysis revealed three latent trajectories during childhood: a low/none ACEs group, a medium exposure group, and a high exposure group. Adolescents in the high exposure group manifested a heightened risk of involvement in delinquent behaviors and substance use. They also reported more symptoms of anxiety and depression than their peers in the low/none and medium exposure groups. ConclusionsRepeated exposure to ACEs during childhood can have serious negative repercussions in the lives of adolescents, but maternal closeness may buffer their effects. Scholars should continue to examine the dynamics of ACEs exposure during childhood by using empirical approaches appropriate for identifying age-graded trajectories.

Risk Assessment of Bisphenol A in the Korean General Population

Bisphenol A (BPA) is not a natural substance but is produced artificially during the manufacturing of various plastics. Exposure to (BPA) is a pervasive and growing concern. BPA has recently been classified as a substance of great concern by the European Union (EU). BPA is suspected to be associated with several chronic human health effects. In this study, the estimated total BPA exposure levels were based on biomonitoring of the general population, and exposure levels ranged from a mean of 0.031 to 0.042 µg/kg body weight (bw)/day, reaching up to 0.104 µg/kg bw/day in the high-exposure population. When comparing the exposure levels of BPA to some toxicological effects, such as immunotoxicity and thyroid function, a sufficient exposure margin was not secured in the high-exposure group. Food is considered the main source of exposure for the general population, but other sources of exposure may exist in the high-exposure group. As humans are primarily exposed to BPA through food, water, house dust, skin contact, and air, integrated risk management is required to reduce BPA exposure. In addition, it is considered necessary to develop a new methodology for human health evaluation in response to low-dose exposure to BPA.

Post-modified ligand exchange of UiO-66 with high-exposure rhodanine sites for enhancing the rapid and selective capture of Ag(I) from wastewater

Highly efficient capturing of silver from wastewater is critical for environmental and economic sustainability but remains significantly challenging to achieve fast kinetics and precise selectivity. Herein, we present two approaches based on rhodanine (Rd)-modified UiO-66 including post-modified ligand exchange for UiO-66-Rdp-m and in-situ solvothermal for UiO-66-Rdi-s. The resultant UiO-66-Rdp-m and UiO-66-Rdi-s perform maximum adsorption capacity of 120 and 109 mg·g−1, respectively, which are both about 6 times higher than pristine UiO-66. Benefitting from high-exposure Rd groups over the surface, UiO-66-Rdp-m exhibits about 3 times faster kinetic adsorption and nearly 15 times higher maximum selectivity coefficient than UiO-66-Rdi-s. Experiment and calculation demonstrate that the excellent performance of Rd-modified UiO-66 is dominantly owing to S chelation in the Rd group. In addition, site energy distributions of the Dubinin-Ashtakhov isotherm model confirm that UiO-66-Rdp-m has more effective sites for Ag(I) adsorption relative to UiO-66-Rdi-s. While a higher density of Rd outside the UiO-66-Rdp-m provides a larger coordination number of S/Ag (1.41) than UiO-66-Rdi-s (0.59), which is attributed to its sufficient exposed active S sites for multidentate coordination of Ag(I), thus significantly enhancing adsorption rate and selectivity. These findings are exploited to shed new insight into the design of adsorbents for the efficient recycling of noble metals from water.

Association between anlotinib trough plasma concentration and treatment outcomes in advanced non-small-cell lung cancer.

Efficacy and toxicities of anlotinib (ANL) show large inter-patient variation, which may partly be explained by differences in ANL exposure. Exposure-response/toxicities relationship have not been investigated for ANL. Therefore, the aim of the present study was to explore the association between the trough plasma concentration (Ctrough) of ANL and treatment outcomes in Chinese patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who started third-line or further ANL alone therapy between January 2021 and October 2022. This study examined the ANL Ctrough and clinical response evaluation at day 43 after initiation of ANL treatment. We evaluated the association between the ANL Ctrough and clinical efficacy and toxicities. Additionally, this study defined patients with complete response (CR), partial response (PR) and stable disease (SD) as responder. The receiver-operating characteristic (ROC) curve combined with Youden index was identify the potential threshold value of ANL Ctrough for the responder. 52 patients were evaluated for analyses. The median ANL Ctrough was 11.45ng/ml (range, 3.69-26.36 ng/ml). The ANL Ctrough values in the PR group (n=6, 15.51 ng/ml (range, 8.19-17.37 ng/ml)) was significantly higher than in the PD group (n=8, 7.44 ng/ml (range, 5.41-14.69 ng/ml), p=0.001). The area under the ROC curve (AUCROC) was 0.76 (95% confidence interval (CI), 0.58-0.93; p=0.022) and threshold value of ANL Ctrough predicting responder was 10.29 ng/ml (sensitivity 65.9% and specificity 87.5%, the best Youden index was 0.53). The disease control rate (DCR) was 84.6%, and DCR was significantly higher in the high-exposure group (≥10.29ng/ml) than low-exposure group (<10.29ng/ml) (96.67% vs 68.18%, p=0.005). Although there was no significant difference in ANL Ctrough between grade ≥ 3 and grade ≤2 toxicities, the incidence of any grade hand-foot syndrome (70.0% vs 36.36%, p=0.016) and thyroid-stimulating hormone elevation (53.33% vs 22.73%, p =0.026) was significantly higher in the high-exposure group compared with the low-exposure group. Considering these results, we propose that maintaining ANL Ctrough ≥ 10.29ng/ml was important for achieving the response in advanced NSCLC patients treated with ANL.