Air concentrations of volatile organic compounds associated with conventional and "green" cleaning products in real-world and laboratory settings.

The use of household cleaning products can result in exposure to potentially hazardous volatile and semi-volatile organic compounds (VOCs and SVOCs). "Green" cleaning products have become increasingly available, but there is no official "green" standard, and it is difficult for consumers to know what chemicals they may be exposed to while cleaning. We measured air concentrations of 46 VOCs and SVOCs of concern released from conventional and "green" cleaning products during both real-world household cleaning and a controlled chamber environment, with a focus on chemicals that might increase women's risk of breast cancer, including possible carcinogens, reproductive/developmental toxicants, or endocrine disruptors. Air samples were analyzed using gas chromatography-mass spectrometry and high-performance liquid chromatography. First, in a study of 50 women cleaning their own homes using either conventional or "green" cleaning products, we recorded the products used and collected air samples from the breathing zone to determine whether specific products or types of products were associated with increased concentrations of specific VOCs and SVOCs. The results showed that women who used conventional bleach products, disinfecting wipes, and dish soap had higher breathing zone air concentrations of several VOCs, including chloroform, carbon tetrachloride, hexaldahyde, and 1,4-dioxane, than women who did not use these products. While fewer "green" products were associated with increases in VOC air concentrations, use of "green" all-purpose cleaners was associated with increases in air concentrations of some fragrance chemicals of concern. In the laboratory, we then selected 9 of the most common conventional products and 7 "green" products used in the in-home study for measurement of the same VOCs using a continuous stirred cylindrical flow-through chamber. We found that 75% of the highest VOC emissions were emitted by conventional cleaning products, but we also identified VOC emissions of concern from green products. VOC emissions in the chamber largely agreed with the modeled associations from real-world cleaning.

Changes in Latina Women's Exposure to Cleaning Chemicals Associated with Switching from Conventional to "Green" Household Cleaning Products: The LUCIR Intervention Study.

BACKGROUND: Household cleaning products may be a significant source of chemical exposures, including carcinogens and suspected endocrine disruptors. OBJECTIVES: We characterized exposures during routine household cleaning and tested an intervention to reduce exposures to cleaning product chemicals. METHODS: The Lifting Up Communities with Interventions and Research (LUCIR) Study is a youth-led, community-based intervention project. Youth researchers conducted personal air monitoring with 50 Latina women while they cleaned their homes with their regular cleaning products (preintervention visit) and then 1 week later while they used "green" cleaning products provided by the study (postintervention visit). Air samples were analyzed for volatile and semivolatile organic compounds using gas chromatography-mass spectrometry and high-performance liquid chromatography. We compared pre- and postintervention air concentrations of 47 chemicals of concern, selected because they were on California's Proposition 65 list of carcinogens or reproductive/developmental toxicants or were suspected endocrine disruptors. Youth researchers were integrally involved in the study design, data collection, interpretation, and dissemination of findings. RESULTS: We observed statistically significant decreases in air concentrations of 17 chemicals of concern when participants switched to green cleaning products, including decreases in geometric mean concentrations of 1,4-dioxane (-46.4%), chloroform (-86.7%), benzene (-24.8%), naphthalene (-40.3%), toluene (-24.2%), and hexane (-35.5%). We observed significant increases in air concentrations of three fragrance compounds: the plant-derived terpene, beta-myrcene (221.5%), and the synthetic musks celestolide (31.0%) and galaxolide (79.6%). Almost all participants (98%) said the replacement products worked as well as their original products, and 90% said that they would consider buying the replacement products in the future. DISCUSSION: This study demonstrates that choosing cleaning products that are marketed as green may reduce exposure to several carcinogens and endocrine disruptors. Future studies should determine whether use of unscented green products would further reduce exposure to terpenes and musks. https://doi.org/10.1289/EHP8831.

"Freedom to Breathe": Youth Participatory Action Research (YPAR) to Investigate Air Pollution Inequities in Richmond, CA.

Air pollution is a major contributor to human morbidity and mortality, potentially exacerbated by COVID-19, and a threat to planetary health. Participatory research, with a structural violence framework, illuminates exposure inequities and refines mitigation strategies. Home to profitable oil and shipping industries, several census tracts in Richmond, CA are among the most heavily impacted by aggregate burdens statewide. Formally trained researchers from the Center for Environmental Research and Children's Health (CERCH) partnered with the RYSE youth justice center to conduct youth participatory action research on air quality justice. Staff engaged five youth researchers in: (1) collaborative research using a network of passive air monitors to quantify neighborhood disparities in nitrogen dioxide (NO2) and sulfur dioxide (SO2), noise pollution and community risk factors; (2) training in environmental health literacy and professional development; and (3) interpretation of findings, community outreach and advocacy. Inequities in ambient NO2, but not SO2, were observed. Census tracts with higher Black populations had the highest NO2. Proximity to railroads and major roadways were associated with higher NO2. Greenspace was associated with lower NO2, suggesting investment may be conducive to improved air quality, among many additional benefits. Youth improved in measures of empowerment, and advanced community education via workshops, Photovoice, video, and "zines".

A new 18S rRNA phylogeny of uncultured predacious fungi (Zoopagales).

Previous molecular phylogenetic studies have shown that families in Zoopagales are not monophyletic. To test the monophyly of genera and species in the order, we used a single-cell approach to generate nuclear 18S rRNA (18S) sequences for 10 isolates representing nine taxa. We provide the first sequences for the genus Zoopage and additional sequences for taxa in Cocholonema, Acaulopage, and Zoophagus. Our results reveal that Zoophagus, Zoopage, and Acaulopage tetraceros are not monophyletic. We conclude that morphology alone is not sufficient to delineate genera and species in the order and encourage studies that increase genetic sampling of taxa including type species.

Determinants of pesticide concentrations in silicone wristbands worn by Latina adolescent girls in a California farmworker community: The COSECHA youth participatory action study.

Personal exposure to pesticides has not been well characterized, especially among adolescents. We used silicone wristbands to assess pesticide exposure in 14 to 16 year old Latina girls (N = 97) living in the agricultural Salinas Valley, California, USA and enrolled in the COSECHA (CHAMACOS of Salinas Examining Chemicals in Homes and Agriculture) Study, a youth participatory action study in an agricultural region of California. We determined pesticide concentrations (ng/g/day) in silicone wristbands worn for one week using gas chromatography electron capture detection and employed gas chromatography mass spectrometry to determine the presence or absence of over 1500 chemicals. Predictors of pesticide detections and concentrations were identified using logistic regression, Wilcoxon rank sum tests, and Tobit regression models. The most frequently detected pesticides in wristbands were fipronil sulfide (87%), cypermethrin (56%), dichlorodiphenyldichloroethylene (DDE) (56%), dacthal (53%), and trans-permethrin (52%). Living within 100 m of active agricultural fields, having carpeting in the home, and having an exterminator treat the home in the past six months were associated with higher odds of detecting certain pesticides. Permethrin concentrations were lower for participants who cleaned their homes daily (GM: 1.9 vs. 6.8 ng/g/day, p = 0.01). In multivariable regression models, participants with doormats in the entryway of their home had lower concentrations (p < 0.05) of cypermethrin (87%), permethrin (99%), fipronil sulfide (69%) and DDE (75%). The results suggest that both nearby agricultural pesticide use and individual behaviors are associated with pesticide exposures.

High-fraction brookite films from amorphous precursors.

Structure-specific synthesis processes are of key importance to the growth of polymorphic functional compounds such as TiO2, where material properties strongly depend on structure as well as chemistry. The robust growth of the brookite polymorph of TiO2, a promising photocatalyst, has been difficult in both powder and thin-film forms due to the disparity of reported synthesis techniques, their highly specific nature, and lack of mechanistic understanding. In this work, we report the growth of high-fraction (~95%) brookite thin films prepared by annealing amorphous titania precursor films deposited by pulsed laser deposition. We characterize the crystallization process, eliminating the previously suggested roles of substrate templating and Na helper ions in driving brookite formation. Instead, we link phase selection directly to film thickness, offering a novel, generalizable route to brookite growth that does not rely on the presence of extraneous elements or particular lattice-matched substrates. In addition to providing a new synthesis route to brookite thin films, our results take a step towards resolving the problem of phase selection in TiO2 growth, contributing to the further development of this promising functional material.

Discovery of selective and potent inhibitors of gram-positive bacterial thymidylate kinase (TMK).

Thymidylate kinase (TMK) is an essential enzyme in bacterial DNA synthesis. The deoxythymidine monophosphate (dTMP) substrate binding pocket was targeted in a rational-design, structure-supported effort, yielding a unique series of antibacterial agents showing a novel, induced-fit binding mode. Lead optimization, aided by X-ray crystallography, led to picomolar inhibitors of both Streptococcus pneumoniae and Staphylococcus aureus TMK. MICs < 1 µg/mL were achieved against methicillin-resistant S. aureus (MRSA), S. pneumoniae, and vancomycin-resistant Enterococcus (VRE). Log D adjustments yielded single diastereomers 14 (TK-666) and 46, showing a broad antibacterial spectrum against Gram-positive bacteria and excellent selectivity against the human thymidylate kinase ortholog.

Cystic pancreatic neoplasm in pregnancy: a case report and review of the literature.

Mucinous cystic neoplasms of the pancreas are rare tumors that tend to occur in young women. They are thought to be responsive to sex hormones. We report a case of a 32-year-old pregnant woman with a 7-month history of pain and a left upper quadrant abdominal mass. She arrived at the emergency department with exacerbation of her symptoms during week 15 of gestation. Findings from ultrasonography and magnetic resonance imaging suggested a pancreatic cyst. Percutaneous aspiration of the cyst fluid yielded mucinous fluid with an elevated carcinoembryonic antigen level. The patient underwent a spleen-preserving distal open pancreatectomy. We present herein a brief review of the current literature on mucinous cystic neoplasms during pregnancy. On the basis of our experience and the existing knowledge of this condition, we advocate resection during the second trimester with splenic preservation.

Novel preparation and characterization of a trastuzumab-streptavidin conjugate for pre-targeted radionuclide therapy.

INTRODUCTION: This study describes a novel and convenient route for the preparation of a trastuzumab-streptavidin conjugate such as might be used in a pre-targeting system and its in-vitro and in-vivo evaluation. METHODS: Trastuzumab was irradiated with UV light in the presence of stannous ions to reduce a number of the disulfide bridges to free thiol groups. A range of irradiation times were studied in order to quantify the number of thiols produced and to optimize the reduction process. The conjugate was then prepared by reaction with succinimidyl 4-(N-maleimidomethy cyclohexane)-1-carboxylate (SMCC)-linked streptavidin. RESULTS: Initial conjugation reactions in phosphate buffer were inefficient, producing low conjugate yields, but conjugation reactions in triethanolamine-based buffer showed greatly increased conjugation yields. A high purity product (approximately 100%) was obtained following purification by gel-filtration HPLC as determined by subsequent size exclusion HPLC analysis. The conjugate was shown to possess an essentially identical immunoreactivity to that of the native, unconjugated antibody and an unaltered biotin binding stoichiometry. Shedding and internalization by Her-2-expressing cells were low and the uptake in vivo by Her-2-expressing xenografts in nude mice was similar to that of labelled antibody. CONCLUSION: Our results demonstrate a new, simple and effective method for the successful synthesis of antibody-streptavidin conjugates which could also be applied to many other heterodimeric protein conjugation reactions.

Synthesis of trimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrates and dimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrate lactones-an assay for the stereochemical outcome of the reaction catalysed both by homocitrate synthase and by the Nif-V protein.

Trimethyl (3R)-homocitrate 17, trimethyl (2S,3R)-[2-2H1]-homocitrate 17a and (2R,3R)-[2-2H1]-homocitrate 17b, as well as dimethyl (3R)-homocitrate lactone 18, (2S,3R)-[2-2H1]-homocitric lactone 18a and (2R,3R)-[2-2H1]-homocitric lactone 18b have been synthesised. D-quinic acid 12 was used as the source of the (3R)-centre in the unlabelled target compounds 17 and 18. (2)-Shikimic acid 19 and the (2)-[2-2H]-shikimic acid derivative 32 respectively were used in the synthesis of the labelled compounds. In the latter syntheses, Sharpless directed epoxidation of the olefin in the 5-deoxy ester diols 23 and 35 ensured a reaction from the same face as the allylic and homoallylic alcohols, and the reduction of the protected epoxides 25 and 37 ensured that the label was introduced in a stereoselective manner. The 1H NMR spectra of the labelled products present an assay for the stereochemistry of the biological reactions catalysed by homocitrate synthase and by the protein from the nifV gene.

PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders.

Variation in genes encoding costimulatory molecules expressed on lymphocytes has been expected to contribute to the genetic component of inflammatory disease, but only the gene encoding the inhibitory protein, CTLA-4, seems consistently to confer disease susceptibility. Studies in murine models implicate the inhibitory product of the pd1 gene, programmed death-1, in the maintenance of peripheral tolerance to self-antigens. We identify 22 single-nucleotide polymorphisms (SNPs) in the equivalent human gene, PDCD1, a number of which show significant associations with the specific immunoglobulin E response to grass allergens in atopic individuals. Stepwise analyses indicate that four of the disease-associated SNPs have independent effects. The two most common haplotypes show positive and negative associations but rarer haplotypes are also likely to be of influence. In a case-control study, multiple regression analysis of genotypic data implies that PDCD1 also confers susceptibility to rheumatoid arthritis. Along with work linking PDCD1 with susceptibility to another autoimmune condition, systemic lupus erythematosus, our data identify PDCD1 as a second immunomodulatory gene with pleiotropic effects in human disease. Genes encoding negative regulators may generally confer a significant fraction of the genetic risk associated with inherited inflammatory disorders.

Synthesis and biological activity of a novel class of pyridazine analogues as non-competitive reversible inhibitors of protein tyrosine phosphatase 1B (PTP1B).

A series of novel pyridazine analogues were prepared and the structure-activity relationship of their behavior as inhibitors of PTP1B was evaluated. Most of the analogues had potencies in the low micromolar range. The in vitro kinetics of this compound series demonstrated that they were reversible non-competitive binders. This indicates that there may exist another site in the enzyme through which enzyme activity can be inhibited, which is not a recognized interaction domain. Some of the analogues exhibited high selectivity for other PTPases, for example, compound 12 mp showed 20-fold selectivity for PTP1B (IC50=5.6 microM) versus both TCPTP and LAR (>100 microM, respectively). In contrast to many tyrosine phosphatase mimetic inhibitors, this compound class lacks negative charge and thus showed high permeability across cell membranes. Selective analogues in the series were analyzed in an in vitro cellular assay, which showed increased insulin-stimulated insulin receptor phosphorylation.

Heart rate and oxygen uptake relationship: a comparison of loaded marching and running in women.

Heart rate (beats.min-1; fc) measured during marching with a load is often used to predict the oxygen cost (l.min-1; VO2) of the activity. The prediction comes from the fc/VO2 relationship determined from laboratory measures of fc and VO2 during treadmill running. Studies in men have suggested that this may not be appropriate although this has yet to be examined in women. This study, therefore, compared the fc/VO2 relationship between loaded marching and maximal running protocols in women. Sixteen female subjects [mean (SD), age 21.9 (2.3) years, height 6 (0.06) m, weight 62.6 (7.6) kg] had their fc (from three-lead chest electrodes) and VO2 measured first during standard treadmill run protocols, and again 1 week later during loaded marching protocols. The slopes and intercepts determined from linear regression of fc on VO2 for each individual for each protocol were compared as were the maximal fc(fcmax), VO2 and ratings of perceived exertion (RPE) from the last work period of each protocol in paired t-tests. The fc/VO2 slopes (P < 0.01) and intercepts (P < 0.05) differed significantly between loaded marching and running. fcmax for loaded marching were 90% of fcmax for running (P < 0.01) and VO2peak for loaded marching were 80% of those for running (P < 0.01). However, RPE at the final levels for the two protocols were not significantly different. The data suggest that in women the fc/VO2 relationships for loaded marching and for running are different. This difference is similar to that found in men when speed is held constant and the load and gradient are varied. The results suggest that it would be erroneous to use fc and VO2 measured during running protocols in the laboratory to estimate energy expenditure and work intensity during loaded marching in the field.