The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the ...regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1-3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.
Dosimetry models can be used to predict the dose of inhaled material, but they require several parameters including particle size distribution. The reported particle size distributions for aerosols ...from electronic nicotine delivery system (ENDS) products vary widely and don't always identify a specific product. A low-flow cascade impactor was used to determine the particle size distribution mass median aerodynamic diameter (MMAD); geometric standard deviation (GSD) from 20 different cartridge based ENDS products. To assess losses and vapor phase amount, collection efficiency of the system was measured by comparing the collected mass in the impactor to the difference in ENDS product mass. The levels of nicotine, glycerin, propylene glycol, water, and menthol in the formulations of each product were also measured. Regardless of the ENDS product formulation, the MMAD of all tested products was similar and ranged from 0.9 to 1.2 μm with a GSD ranging from 1.7 to 2.2. There was no consistent pattern of change in the MMAD and GSD as a function of number of puffs (cartridge life). The collection efficiency indicated that 9%–26% of the generated mass was deposited in the collection system or was in the vapor phase. The particle size distribution data are suitable for use in aerosol dosimetry programs.
•ENDS product formulation did not affect the MMAD or GSD.•MMAD and GSD were not affected by puff count.•Vapor phase and losses range from 9% to 26% of the generated mass.•Particle size distribution data are suitable for use in aerosol dosimetry programs.
A unique adult human mouth/throat physical model has been developed to study e-cigarette aerosol dynamics during inhalation. The 3D printed physical model was created from the CT scan of a 28 yr. old ...healthy male. Internal walls of the physical model were lined with a thin layer of cotton gauze that can be saturated with water to replicate the high relative humidity conditions in a human Oral/Pharyngeal cavity. Aerosol hygroscopic growth and deposition inside the physical model from a cartomizer style e-cigarette using a prototype e-liquid formulation was determined by measuring cumulative aerosol mass from five puffs (gravimetric) and for individual constituents (propylene glycol, glycerol, and nicotine) from a single puff (GC/MS analysis). Measurements were taken at constant temperature of 37 °C under both wet and dry inner wall conditions for a for a 3-sec. 55 mL puff. The condition of holding aerosol inside the physical model without airflow for a duration of 3-sec. was also included. For the same puffing conditions of 3-sec puff of 55 mL and a 3-sec. puff hold time, dry wall conditions resulted in a mean aerosol mass loss of 20.9 ± 3.8%, while the total aerosol mass was increased by 150.9 ± 19% under wet wall condition when compared to total aerosol mass entering the physical model entrance. The dramatic increase is due to water vapor uptake by the aerosol particles when flowing through the wetted physical model. Aerosol evolution of individual chemical constituent analysis appeared to vary as a function of volatility.
Mobile smartphones are rapidly emerging as an effective means of communicating with many Americans. Using mobile applications (apps), they can access remote databases, track time and location, and ...integrate user input to provide tailored health information.
A smartphone mobile app providing personalized, real-time sun protection advice was evaluated in a randomized clinical trial.
The trial was conducted in 2012 and had a randomized pretest-posttest controlled design with a 10-week follow-up. Data were collected from a nationwide population-based survey panel. A sample of 604 non-Hispanic and Hispanic adults from the Knowledge Panel 18 years or older who owned an Android smartphone were enrolled.
The mobile app provided advice on sun protection (ie, protection practices and risk of sunburn) and alerts (to apply or reapply sunscreen and get out of the sun), hourly UV Index, and vitamin D production based on the forecast UV Index, the phone's time and location, and user input.
Percentage of days using sun protection and time spent outdoors (days and minutes) in the midday sun and number of sunburns in the past 3 months were collected.
Individuals in the treatment group reported more shade use (mean days staying in the shade, 41.0% vs 33.7%; P = .03) but less sunscreen use (mean days, 28.6% vs 34.5%; P = .048) than controls. There was no significant difference in number of sunburns in the past 3 months (mean, 0.60 in the treatment group vs 0.62 for controls; P = .87). Those who used the mobile app reported spending less time in the sun (mean days keeping time in the sun to a minimum, 60.4% for app users vs 49.3% for nonusers; P = .04) and using all protection behaviors combined more (mean days, 39.4% vs 33.8%; P = .04).
The mobile app improved some sun protection. Use of the mobile app was lower than expected but associated with increased sun protection. Providing personalized advice when and where people are in the sun may help reduce sun exposure.
Mobile applications on smartphones can communicate a large amount of personalized, real-time health information, including advice on skin cancer prevention, but their effectiveness may be affected by ...whether recipients can be convinced to use them.
To evaluate a smartphone mobile application (Solar Cell) delivering real-time advice about sun protection for a second time in a randomized clinical trial.
A previous trial conducted in 2012 used a randomized pretest-posttest design. For the present trial, we collected data from a volunteer sample of 202 adults 18 years or older who owned a smartphone. Participants were recruited nationwide through online promotions. Screening procedures and a 3-week run-in period were added to increase the use of the mobile application. We conducted follow-ups at 3 and 8 weeks after randomization to examine the immediate and the longer-term effects of the intervention.
Use of the mobile application. The application gave feedback on sun protection (ie, sun-safety practices and the risk for sunburn) and alerted users to apply or to reapply sunscreen and to get out of the sun. The application also displayed the hourly UV Index and vitamin D production based on the forecast UV Index, time, and location.
Percentage of days with the use of sun protection, time spent outdoors in the midday sun (days and hours), and the number of sunburns in the last 3 months.
Participants in the intervention group used wide-brimmed hats more at 7 weeks than control participants (23.8% vs 17.4%; F = 4.07; P = .045). Women who used the mobile application reported using all sun protection combined more than men (46.4% vs 43.3%; F = 1.49; P = .04), whereas men and older individuals reported less use of sunscreen (32.7% vs 35.5%; F = 5.36; P = .02) and hats (15.6% vs 17.9%; F = 4.72; P = .03).
The mobile application initially appeared to confer weak improvement of sun protection. Use of the mobile application was greater than in a previous trial and was associated with greater sun protection, especially among women. Strategies to increase the use of the mobile application are needed if the application is to be deployed effectively to the general adult population.
Purpose - There is a paucity of literature considering horizontal collaboration among grocery retailers, suppliers, and third-party logistics (3PL) providers. This paper seeks to investigate benefits ...of and barriers to the use of fourth-party logistics (4PL) management as a catalyst for horizontal collaboration.Design methodology approach - Three suppliers, three logistics service providers (LSPs), and one grocery retailer participated in semi-structured interviews for this exploratory qualitative study.Findings - Large LSPs can establish 4PL management but the significant investment required to do so is a deterrent. Interviewees believed 4PL would negatively influence the grocery retailer-supplier dynamic but simultaneously would provide key potential benefits. Retaining supply chain control means more to grocery retailers than cost efficiencies realised through horizontal collaboration.Research limitations implications - Fierce competition among major grocery chains means that most are unwilling to participate in studies of their systems, which restricts the research scope.Practical implications - Some stakeholders want deeper integration into grocery supply networks, and the 4PL model could apply to diverse sectors and circumstances. This study shows that barriers to such integration are created by power plays among lead stakeholders in grocery retailing that inhibit horizontal collaboration regardless of cost or other benefits.Originality value - The study investigates an under-researched aspect of horizontal supply chain collaboration in the highly relevant retail grocery sector: a high volume, mass market industry that requires an enormous logistics infrastructure and highly embedded networks of relationships.
Diagnosis-code-based algorithms to identify fall injuries in Medicare data are useful for ascertaining outcomes in interventional and observational studies. However, these algorithms have not been ...validated against a fully external reference standard, in ICD-10-CM, or in Medicare Advantage (MA) data.
We linked self-reported fall injuries leading to medical attention (FIMA) from the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial (reference standard) to Medicare fee-for-service (FFS) and MA data from 2015-2019. We measured the area under the receiver operating characteristic curve (AUC) based on sensitivity and specificity of a diagnosis-code-based algorithm against the reference standard for presence or absence of ≥1 FIMA within a specified window of dates, varying the window size to obtain points on the curve. We stratified results by source (FFS versus MA), trial arm (intervention versus control), and STRIDE's ten participating healthcare systems.
Both reference standard data and Medicare data were available for 4941 (of 5451) participants. The reference standard and algorithm identified 2054 and 2067 FIMA, respectively. The algorithm had 45% sensitivity (95% confidence interval CI, 43%-47%) and 99% specificity (95% CI, 99%-99%) to identify reference standard FIMA within the same calendar month. The AUC was 0.79 (95% CI, 0.78-0.81) and was similar by FFS or MA data source or trial arm, but showed variation among STRIDE healthcare systems (AUC range by healthcare system, 0.71 to 0.84).
An ICD-10-CM algorithm to identify fall injuries demonstrated acceptable performance against an external reference standard, in both MA and FFS data.
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