Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod.

Maternal diet disrupts the placenta-brain axis in a sex-specific manner.

High maternal weight is associated with detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression and communicative disorders. Despite widespread acknowledgement of sex biases in the development of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we show that a maternal high-fat diet causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation contributes to sex-specific behavioural outcomes in offspring.

Prediction of potential passive exposure from commercial electronic nicotine delivery systems using exhaled breath analysis and computational fluid dynamic techniques.

Use of computational fluid dynamic (CFD) modeling to predict temporal and spatial constituent exposure for non-electronic nicotine delivery systems (ENDS) users (passive exposure) provides a more efficient methodology compared to conducting actual exposure studies. We conducted a clinical study measuring exhaled breath concentrations of glycerin, propylene glycol, nicotine, benzoic acid, formaldehyde, acetaldehyde, acrolein, menthol and carbon monoxide from use of eight different commercial ENDS devices and a non-menthol and menthol cigarette. Because baseline adjusted levels of other constituents were not consistently above the limit of detection, the mean minimum and maximum per puff exhaled breath concentrations (= 20/product) of glycerin (158.

Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers.

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.

The American College of Surgeons Response to the COVID-19 Pandemic (Part II) : Advocacy and Public Policy.

From the onset of the COVID-19 global pandemic of 2020, the American College of Surgeons (ACS) has been a leader in disseminating credible information on the clinical and scientific aspects of the disease. As governmental regulations enforced the closure of hospitals and operating rooms to elective surgical cases as part of its "shelter-in-place" public lockdown policies, the ACS brought specialty societies together to create guidelines to protect patients and preserve surgical quality. Federal agencies made available financial aid programs to mitigate the economic impact of the outbreak.

Insights on CTC Biology and Clinical Impact Emerging from Advances in Capture Technology.

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.

Single-Cell Tracking of Breast Cancer Cells Enables Prediction of Sphere Formation from Early Cell Divisions.

The 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.

Thiodipeptides targeting the intestinal oligopeptide transporter as a general approach to improving oral drug delivery.

The broad substrate capacity of the intestinal oligopeptide transporter, PepT1, has made it a key target of research into drug delivery. Whilst the substrate capacity of this transporter is broad, studies have largely been limited to small peptides and peptide-like drugs. Here, we demonstrate for the first time that a diverse range of drugs can be targeted towards transport by PepT1 using a hydrolysis resistant carrier.

Real-time scratch assay reveals mechanisms of early calcium signaling in breast cancer cells in response to wounding.

Aggressive cellular phenotypes such as uncontrolled proliferation and increased migration capacity engender cellular transformation, malignancy and metastasis. While genetic mutations are undisputed drivers of cancer initiation and progression, it is increasingly accepted that external factors are also playing a major role. Two recently studied modulators of breast cancer are changes in the cellular mechanical microenvironment and alterations in calcium homeostasis.

Impact of an integrated intervention program on atorvastatin adherence: a randomized controlled trial.

Background: This trial evaluated the effectiveness of an integrated intervention program that included a 3-to-5-minute nurse counseling session, copay relief cards, and a monthly newsletter on adherence to atorvastatin treatment.

Methods And Results: A prospective, integrated (composed of nurse counseling, adherence tip sheet, copay relief card, opportunity to enroll in 12-week cholesterol management program) randomized interventional study was designed involving patients >21 years of age who were prescribed atorvastatin at a large single-specialty cardiovascular physician practice in Illinois from March 2010 to May 2011. Data from the practice's electronic medical record were matched/merged to IMS Health's longitudinal data.

Bioavailability through PepT1: the role of computer modelling in intelligent drug design.

In addition to being responsible for the majority of absorption of dietary nitrogen, the mammalian proton-coupled di- and tri-peptide transporter PepT1 is also recognised as a major route of drug delivery for several important classes of compound, including beta-lactam antibiotics and angiotensin-converting enzyme inhibitors. Thus there is considerable interest in the PepT1 protein and especially its substrate binding site. In the absence of a crystal structure, computer modelling has been used to try to understand the relationship between PepT1 3D structure and function.

The in vitro transport of model thiodipeptide prodrugs designed to target the intestinal oligopeptide transporter, PepT1.

A thiodipeptide carrier system is shown to be effective at enabling a range of covalently bound molecules, including benzyl, benzoyl and ibuprofen conjugates, to be transported via the intestinal peptide transporter PepT1, demonstrating its potential as a rational drug delivery target.

The transmembrane tyrosines Y56, Y91 and Y167 play important roles in determining the affinity and transport rate of the rabbit proton-coupled peptide transporter PepT1.

The mammalian proton-coupled peptide transporter PepT1 is widely accepted as the major route of uptake for dietary nitrogen, as well as being responsible for the oral absorption of a number of classes of drugs, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors. Using site-directed mutagenesis and zero-trans transport assays, we investigated the role of conserved tyrosines in the transmembrane domains (TMDs) of rabbit PepT1 as predicted by hydropathy plots. All the individual TMD tyrosines were substituted with phenylalanine and shown to retain the ability to traffic to the plasma membrane of Xenopus laevis oocytes.

Targeting ketone drugs towards transport by the intestinal peptide transporter, PepT1.

Thiodipeptide prodrugs of the ketone nabumetone are shown to have affinity for, and be transported by, PepT1 in vitro.

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones.

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.