An indoor air quality evaluation in a residential retrofit project using spray polyurethane foam

Understanding of indoor air quality (IAQ) during and after spray polyurethane foam (SPF) application is essential to protect the health of both workers and building occupants. Previous efforts such as field monitoring, micro-chamber/spray booth emission studies, and fate/transport modeling have been conducted to understand the chemical exposure of SPF and guide risk mitigation strategies. However, each type of research has its limitation and can only reveal partial information on the relationship between SPF and IAQ. A comprehensive study is truly needed to integrate the experimental design and analytical testing methods in the field/chamber studies with the mathematical tools employed in the modeling studies. This study aims to bridge this gap and provide a more comprehensive understanding on the impact of SPF to IAQ. The field sampling plan of this research aims to evaluate the airborne concentrations of methylene diphenyl diisocyanate (MDI), formaldehyde, acetaldehyde, propionaldehyde, tris(1-chlor-2-propyl)phosphate (TCPP), trans-1-chloro-3,3,3-trifluoropropene (Solstice^TM), and airborne particles. Modifications to existing MDI sampling and analytical methods were made so that level of quantification was improved. In addition, key fate and transport modeling input parameters such as air changes per hour and airborne particle size distribution were measured. More importantly, TCPP accumulation onto materials was evaluated, which is important to study the fate and transport of semi-volatile organic compounds. The IAQ results showed that after spray application was completed in the entire building, airborne concentrations decreased for all chemicals monitored. However, it is our recommendation that during SPF application, no one should return to the application site without proper personal protection equipment as long as there are active spray activities in the building. The comparison between this field study and a recent chamber study proved surface sorption and particle deposition is an important factor in determining the fate of airborne TCPP. The study also suggests the need for further evaluation by employing mathematical models, proving the data generated in this work as informative to industry and the broader scientific community.     

Enzymatic synthesis of glucuronidated metabolites of two neurological active agents using plant glucuronosyltransferases

Abstract

Glucuronidation is an important and popular metabolic reaction in vivo of drugs. The further evaluation of biological activity and toxicity of glucuronides is necessary in the course of the drug research and development. However, the synthesis of glucuronides is limited by the lack of efficient approach. Herein, we have developed a new glucuronide synthesis method using plant uridine diphosphate-dependent glucuronosyltransferases (UGTs), UGT88D4, UGT88D7, and EpGT8, enabling the convenient preparation for corresponding O-glucuronide metabolites (1a, 2a, 3a, and 3b) in milligram scale of two neurological active agents, IMM-H004 (1) and FLZ (2). Their structures were characterized by spectroscopic data analyses.     

On evaluation of consistency in multi-regional clinical trials

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population). The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, time points of assessment, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. However, the challenge is there is no detailed guidance on the definition of ‘consistency’ and methodology to evaluate it. Therefore, the questions are: how to evaluate consistency and what statistical methods are appropriate to be used for consistency evaluation? In this article, several statistical tests for consistency (similarity) between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation in this article through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given. Other aspects that should be considered for consistency evaluation are also provided.     

Endoscopic molecular imaging of early gastric cancer using fluorescently labeled human H-ferritin nanoparticle

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P?<?0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P?<?0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.     

Maternal Socioeconomic Mobility and Preterm Delivery: A Latent Class Analysis

Objective Growing evidence suggests that maternal socioeconomic mobility (SM) is associated with pregnancy outcomes. Our study investigated the association between maternal SM from childhood to adulthood and the risk of preterm delivery (PTD), and examined heterogeneity of associations by race/ethnicity. Methods In this study, 3019 pregnant women enrolled from 5 Michigan communities at 16–27 weeks’ gestation (1998–2004) provided their parents’ socioeconomic position (SEP) indicators (education, occupation, receipt of public assistance) and their own and child’s father’s SEP indicators (education, occupation, Medicaid status, and household income) at the time of enrollment. Latent class analysis was used to identify latent classes of childhood SEP indicators, adulthood SEP indicators, and SM from childhood to adulthood, respectively. A model-based approach to latent class analysis with distal outcome assessed relations between latent class and PTD, overall and within race/ethnicity groups. Results Three latent classes (low, middle, high) were identified for childhood SEP indicators and adulthood SEP indicators, respectively; while four latent classes (static low, upward, downward, and static high) best described SM. Women with upward SM had decreased odds of PTD (Odds ratio?=?0.60, 95% confidence interval: 0.42, 0.87), compared to those with static low SEP. This SM advantage was true for all women and most pronounced in white/others women. Conclusions Maternal experiences of upward SM may be important considerations when assessing PTD risk. Our results support the argument that policies and programs aimed at improving women’s SEP could lower PTD rates.     

The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl-10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats

Life-threatening diarrhea afflicts a considerable percentage of patients treated with irinotecan, an anticancer agent with effects elicited through its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). The primary detoxification pathway for SN-38 is glucuronidation. The purpose of this study was to evaluate the role that intestinal UDP-glucuronosyltransferases (UGTs) have from hepatic UGTs in modulating this diarrhea. To investigate this, Gunn rats devoid of UGT1A activity were injected with recombinant adenoviral vectors expressing UGT1A1, 1A6, and 1A7, resulting in reconstituted hepatic UGT expression comparable to a heterozygote. Hepatic microsome studies indicated that 4 to 7 days after adenoviral injection, transfected Gunn rats (j/jAV) had SN-38 glucuronide (SN-38G) formation rates three times higher than control heterozygote rats (j+AV). The adenovirus did not impart any glucuronidating capacity to the intestine in j/jAV rats, whereas j+AV rats possessed intestinal UGT function. After the administration of 20 mg/kg/day irinotecan i.p. to j/jAV rats 4 days after adenovirus injection, diarrhea ensued before the fourth irinotecan dose. j+AV rats were spared the diarrhea, and the toxicity was mild compared with the j/jAV rats, as measured by diarrhea scores, weight loss, and histological assessments of the cecum and colon. The pharmacokinetics of irinotecan, SN-38, and SN-38G indicate that the systemic exposure of SN-38 and SN-38G was higher and lower, respectively, in j/jAV rats. Despite this, the biliary excretion of irinotecan and metabolites was similar. Because intestinal UGTs are the main discriminating factor between j/jAV and j+AV rats, their presence seems to be critical for the gastrointestinal protection observed in j+AV rats.     

MiR⁃484通过靶向MAPK8抑制人前体脂肪细胞的增殖与分化

目的：探讨miRNA?484在肥胖发生中的作用及其临床意义。方法：利用RT?qPCR 、CCK?8法、油红O染色及甘油三酯定量检测研究miR?484对人脂肪细胞增殖及成脂分化的作用。运用Targetscan7.2对miR?484的下游靶基因进行预测分析,并使用双荧光素酶实验验证miR?484与靶基因的结合,使用Western blot及RT?qPCR验证miR?484对靶基因的作用。结果：miR?484在人脂肪细胞分化成熟过程中逐渐低表达。过表达miR?484抑制人前体脂肪细胞的增殖及分化,而沉默miR?484与过表达作用相反。生物信息学预测发现MAPK8是miR?484的下游靶基因,且miR?484可抑制其mRNA及蛋白表达,同时过表达MAPK8可部分挽救miR?484对人前体脂肪细胞增殖分化的抑制。结论：miR?484可以通过抑制MAPK8的表达从而抑制人前体脂肪细胞的增殖与成脂分化。     

2型糖尿病合并超重肥胖患者血清Irisin水平变化研究

背景 肥胖会导致胰岛素抵抗（IR）的发生进而引发2型糖尿病（T2DM）,严重影响人类健康。鸢尾素（irisin）是一种新发现的肌肉和脂肪因子,在代谢调控中具有重要作用,T2DM合并超重肥胖患者的血清irisin水平会出现何种变化值得研究。 目的 观察T2DM超重肥胖患者血清irisin水平情况,并探讨血清irisin水平变化的影响因素。 方法 选取2019年12月至2021年6月于安徽医科大学第一附属医院内分泌科住院治疗的T2DM患者119例,根据体质指数（BMI）分为糖尿病超重肥胖组（n=78）和糖尿病体质量正常组（n=41）。另选取同期于本院体检且BMI正常的健康者为对照组（n=52）。比较三组受试者一般资料、实验室检查指标及血清irisin水平,采用Spearman秩相关分析探究血清irisin水平与一般资料及实验室检查指标的相关性,采用多元线性回归分析探究血清irisin水平的影响因素。 结果 三组收缩压（SBP）、舒张压（DBP）、BMI、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、糖化血红蛋白（HbA1c）、空腹血糖（FBG）、空腹胰岛素（FINS）、稳态胰岛素抵抗指数（HOMA-IR）比较,差异均有统计学意义（P<0.05）。糖尿病体质量正常组血清irisin水平低于对照组,糖尿病超重肥胖组血清irisin水平低于对照组、糖尿病体质量正常组（P<0.05）。Spearman秩相关分析结果显示,血清irisin水平与HDL-C呈正相关（rs=0.304,P<0.05）,与SBP、DBP、BMI、TG、HbA1c、FBG、FINS、HOMA-IR呈负相关（rs值分别为-0.271、-0.420、-0.372、-0.164、-0.418、-0.348、-0.293、-0.348,P<0.05）。多元线性回归分析结果显示,DBP〔b=-0.049,P=0.011〕、HbA1c〔b=-0.156,P=0.009〕、FINS〔b=-0.21,P=0.038〕是血清irisin水平的影响因素。 结论 T2DM患者血清irisin水平较健康者明显降低,尤其是合并超重肥胖患者,且血清irisin水平与血压、BMI、血脂、血糖及IR等因素存在一定关系。