Introduction Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual use is associated with decreases in exposure to toxicants. Methods This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group, and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers. Results In JUUL groups, median percent reductions in primary BOEs (Day 6–Baseline) were 90%– ≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps<0.025). Median reductions in primary BOEs in the Dual Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs. Conclusion This study suggests that use of JUUL as a complete or partial substitute (i.e., dual use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking. Implications This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System (“JUUL”) in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.
Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) have been shown to correlate negatively with patient survival. Actual CTC counts before and after treatment can be used to aid in the prognosis of patient outcomes. The presence of circulating tumor materials (CTMat) can advertise the presence of metastasis before clinical presentation, enabling the early detection of relapse. Importantly, emerging evidence is indicating that cancer treatments can actually increase the incidence of CTCs and metastasis in pre-clinical models. Subsequently, the study of CTCs, their biology and function are of vital importance. Emerging technologies for the capture of CTC/CTMs and CTMat are elucidating vitally important biological and functional information that can lead to important alterations in how therapies are administered. This paves the way for the development of a “liquid biopsy” where treatment decisions can be informed by information gleaned from tumor cells and tumor cell debris in the blood.
SummaryThe mammosphere assay has become widely employed to quantify stem-like cells in a population. However, the problem is there is no standard protocol employed by the field. Cell seeding densities of 1,000 to 100,000 cells/mL have been reported. These high densities lead to cellular aggregation. To address this, we have individually tracked 1,127 single MCF-7 and 696 single T47D human breast tumor cells by eye over the course of 14 days. This tracking has given us detailed information for the commonly used endpoints of 5, 7, and 14 days that is unclouded by cellular aggregation. This includes mean sphere sizes, sphere-forming efficiencies, and a well-defined minimum size for both lines. Importantly, we have correlated early cell division with eventual sphere formation. At 24 hr post seeding, we can predict the total spheres on day 14 with 98% accuracy in both lines. This approach removes cell aggregation and potentially shortens a 5- to 14-day assay to a 24 hours.
ABSTRACT. A number of studies have indicated that the emphasis on low shear rate viscosity and rouleaux-related pherheologic properties of neonatal blood are different from nomena. those of the adult. The frequent administration of blood components to the neonate during intensive care make it important that these differences be established and their MATERIALS AND METHODS causes understood. The purpose of this study was to make a detailed comparison of the rheologic properties of nee-Blood was obtained from healthy adults by venesection, natal and adult blood, with particular emphasis on low and from the umbilical vein of neonates immediately after shear rate viscosity and rouleaux-related phenomena. The clamping of the cord at delivery. In each case, it was anticoaguviscometric data was obtained from seven preterm (PT) lated with 12.5 U/mL of heparin. The babies were all born and l8 term (NT) babies and with those vaginally and did not require resuscitation. They were of normal l8 (A)-In the present study, "iscometry was wt for gestation age. There were too few preterm babies to group performed Over a wide range Of shear rates, O a 3 them according to gestational age, which ranged from 24 to 35 130 s-', and the low shear rate data were with wk, thus all babies of less than 37 wk were classified as preterm. direct measurement of rouleaux formation using the MY-he adults had an age range of 24 to 50 y with a median age of renne Erythrocyte Aggregometer. A major factor leading 30. to the viscometric differences observed was the high hem-1, a pilot survey, the rheologically important variables-hematOcrit in the newborn (46.8 + 2.1% PT, 52.8 + atocrit, plasma viscosity, and plasma fibrinogen concentration-6-1% NT, 44-1 * 2.5% A 40.5 + A females)-were compared between pre-and normal term babies and adults.ow ever, this tended to be compensated for by the lower This was followed by a more comprehensive hemorheologic plasma (Iso5 * 0.07 mPas PT, * 0-14 mPas study that included the measurement of blood viscosity over a NT,* O e o 8 mPas A-n0 sex difference) and reduced wide range of shear rates. These viscometric studies were made rOuleaux in the and more according to the ICSH Guidelines (7) on blood at native hemamarked in the preterm baby. The lowered levels red tocrit and, after adjustment by adding or subtracting autologous aggregation were found not to be due to cellular differences plasma, at 45%. The hematocrit was measured by microcentribetween the adults and the babies but rather to differing fugation without correction for trapped plasma, plasmaThe presence the fetal variant In some experiments, washed cells were used. The cells were fibrinogen and low levels of immunoglobulins, especially washed, by alternate centrifugation and aspiration of supernaIgM and IgA, are likely be particular imp0rtance. tant, using isotonic PBS. The cells were finally suspended at a (Pediatv Res 25457-460, 1989) hematocrit of 45% in PBS or PBS containing adult human fibrinogen (Kabi Pharmaceuticals, Stockholm, Sweden). Fibrinog...
Aerosol constituent yields have been reported from a wide range of electronic nicotine delivery systems. No comprehensive study has been published on the aerosol constituents generated from the JUUL system. Targeted analyses of 53 aerosol constituents from the four JUUL products currently on the US market (Virginia Tobacco and Menthol flavored e-liquids in both 5.0% and 3.0% nicotine concentration by weight) was performed using non-intense and intense puffing regimens. All measurements were conducted by an ISO 17025 accredited contract research organization. JUUL product aerosol constituents were compared to published values for the 3R4F research cigarette and IQOS Regular and Menthol heated tobacco products. Across the four JUUL products and two puffing regimes, only 10/53 analytes were quantifiable, including only two carbonyls (known propylene glycol or glycerol degradants). The remaining analytes were primary ingredients, nicotine degradants and water. Average analyte reductions (excluding primary ingredients and water) for all four JUUL system aerosols tested were greater than 98% lower than 3R4F mainstream smoke, and greater than 88% lower than IQOS aerosol. In summary, chemical characterization and evaluation of JUUL product aerosols demonstrates a significant reduction in toxicants when compared to mainstream cigarette smoke from 3R4F reference cigarettes or aerosols from IQOS-heated tobacco products.
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