An elastic second skin Yu, Betty; Kang, Soo-Young; Akthakul, Ariya ...
Nature materials,
08/2016, Volume:
15, Issue:
8
Journal Article
Peer reviewed
Open access
We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based ...material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (<40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery and wound dressings.
The use of aqueous film-forming foam (AFFF) to extinguish hydrocarbon-based fires is recognized as a significant source of environmental poly- and perfluoroalkyl substances (PFASs). Although the ...occurrence of select PFASs in soil and groundwater at former fire-training areas (FTAs) at military installations operable since 1970 has been consistently confirmed, studies reporting the occurrence of PFASs at other AFFF-impacted sites (e.g. emergency response locations, AFFF lagoons, hangar-related AFFF storage tanks and pipelines, and fire station testing and maintenance areas) are largely missing from the literature. Further, studies have mostly focused on a single site (i.e., FTAs at military installations) and, thus, lack a comparison of sites with diverse AFFF release history. Therefore, the purpose of this investigation was to evaluate select PFAS occurrence at non-FTA sites on active U.S. Air Force installations with historic AFFF use of varying magnitude. Concentrations of fifteen perfluoroalkyl acids (PFAAs) and perfluorooctane sulfonamide (PFOSA), an important PFOS precursor, were measured from several hundred samples among multiple media (i.e., surface soil, subsurface soil, sediment, surface water, and groundwater) collected from forty AFFF-impacted sites across ten installations between March and September 2014, representing one of the most comprehensive datasets on environmental PFAS occurrence to date. Differences in detection frequencies and observed concentrations due to AFFF release volume are presented along with rigorous data analyses that quantitatively demonstrate phase-dependent (i.e., solid-phase vs aqueous-phase) differences in the chemical signature as a function of carbon chain-length and in situ PFOS (and to a slightly lesser extent PFHxS) formation, presumably due to precursor biotransformation.
Display omitted
•Differences in detection frequencies and observed concentrations due to AFFF release volume are demonstrated.•Background sources of PFOA are evident.•Non-linear carbon chain-length dependence on relative sorption potential is empirically demonstrated.•In situ PFOS and PFHxS formation (40% and 36%, respectively), presumably due to precursor biotransformation, is empirically demonstrated.
While inhibitors of BCL-2 family proteins (BH3 mimetics) have shown promise as anti-cancer agents, the various dependencies or co-dependencies of diverse cancers on BCL-2 genes remain poorly ...understood. Here we develop a drug screening approach to define the sensitivity of cancer cells from ten tissue types to all possible combinations of selective BCL-2, BCL-X
, and MCL-1 inhibitors and discover that most cell lines depend on at least one combination for survival. We demonstrate that expression levels of BCL-2 genes predict single mimetic sensitivity, whereas EMT status predicts synergistic dependence on BCL-X
+MCL-1. Lastly, we use a CRISPR/Cas9 screen to discover that BFL-1 and BCL-w promote resistance to all tested combinations of BCL-2, BCL-X
, and MCL-1 inhibitors. Together, these results provide a roadmap for rationally targeting BCL-2 family dependencies in diverse human cancers and motivate the development of selective BFL-1 and BCL-w inhibitors to overcome intrinsic resistance to BH3 mimetics.
In this article, we examine the impact of digital screen devices, including television, on cognitive development. Although we know that young infants and toddlers are using touch screen devices, we ...know little about their comprehension of the content that they encounter on them. In contrast, research suggests that children begin to comprehend child-directed television starting at ∼2 years of age. The cognitive impact of these media depends on the age of the child, the kind of programming (educational programming versus programming produced for adults), the social context of viewing, as well the particular kind of interactive media (eg, computer games). For children <2 years old, television viewing has mostly negative associations, especially for language and executive function. For preschool-aged children, television viewing has been found to have both positive and negative outcomes, and a large body of research suggests that educational television has a positive impact on cognitive development. Beyond the preschool years, children mostly consume entertainment programming, and cognitive outcomes are not well explored in research. The use of computer games as well as educational computer programs can lead to gains in academically relevant content and other cognitive skills. This article concludes by identifying topics and goals for future research and provides recommendations based on current research-based knowledge.
ABSTRACTRheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular ...disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.
Obesity is a risk factor for pneumonia and acute respiratory distress syndrome.
To determine whether obesity is associated with intubation or death, inflammation, cardiac injury, or fibrinolysis in ...coronavirus disease 2019 (COVID-19).
Retrospective cohort study.
A quaternary academic medical center and community hospital in New York City.
2466 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection over a 45-day period with at least 47 days of in-hospital observation.
Body mass index (BMI), admission biomarkers of inflammation (C-reactive protein CRP level and erythrocyte sedimentation rate ESR), cardiac injury (troponin level), and fibrinolysis (D-dimer level). The primary end point was a composite of intubation or death in time-to-event analysis.
Over a median hospital length of stay of 7 days (interquartile range, 3 to 14 days), 533 patients (22%) were intubated, 627 (25%) died, and 59 (2%) remained hospitalized. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 95% CI, 1.1 to 2.1). This association was primarily observed among patients younger than 65 years and not in older patients (
for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis.
Body mass index was missing for 28% of patients. The primary analyses were conducted with multiple imputation for missing BMI. Upper bounding factor analysis suggested that the results are robust to possible selection bias.
Obesity is associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older.
National Institutes of Health.
The mammalian target of rapamycin (mTOR) senses nutrients and growth factors to coordinate cell growth, metabolism and autophagy. Extensive research has mapped the signaling pathways regulated by ...mTOR that are involved in human diseases, such as cancer, and in diabetes and ageing. Recently, however, new studies have demonstrated important roles for mTOR in promoting the differentiation of adult stem cells, driving the growth and proliferation of stem and progenitor cells, and dictating the differentiation program of multipotent stem cell populations. Here, we review these advances, providing an overview of mTOR signaling and its role in murine and human stem and progenitor cells.
We investigate temporally changing variability amplitudes and the multi-periodicity of the type-I Cepheid Polaris using 161 high-precision radial velocity (RV) and bisector inverse span (BIS) ...measurements based on optical spectra recorded using
Hermes
at the 1.2 m Flemish
Mercator
telescope on La Palma, Canary Islands, Spain. Using an empirical template fitting method, we show that Polaris’ RV amplitude has been stable to within ∼30 m s
−1
between September 2011 and November 2018. We apply the template fitting method to publicly accessible, homogeneous RV data sets from the literature and provide an updated solution of Polaris’ eccentric 29.3 yr orbit. While the inferred pulsation-induced RV amplitudes differ among individual data sets, we find no evidence for time-variable RV amplitudes in any of the separately considered, homogeneous data sets. Additionally, we find that increasing photometric amplitudes determined using SMEI photometry are likely spurious detections due to as yet ill-understood systematic effects of instrumental origin. Given this confusing situation, further analysis of high-quality homogeneous data sets with well-understood systematics is required to confidently establish whether Polaris’ variability amplitude is subject to change over time. We confirm periodic bisector variability periods of 3.97 d and 40.22 d using
Hermes
BIS measurements and identify a third signal at a period of 60.17 d. Although the 60.17 d signal dominates the BIS periodogram, we caution that this signal may not be independent of the 40.22 d signal. Finally, we show that the 40.22 d signal cannot be explained by stellar rotation. Further long-term, high-quality spectroscopic monitoring is required to unravel the complete set of Polaris’ periodic signals, which has the potential to provide unprecedented insights into the evolution of Cepheid variables.
Altered mitochondrial dynamics can broadly impact tumor cell physiology. Using genetic and pharmacological profiling of cancer cell lines and human tumors, we here establish that perturbations to the ...mitochondrial dynamics network also result in specific therapeutic vulnerabilities. In particular, through distinct mechanisms, tumors with increased mitochondrial fragmentation or connectivity are hypersensitive to SMAC mimetics, a class of compounds that induce apoptosis through inhibition of IAPs and for which robust sensitivity biomarkers remain to be identified. Further, because driver oncogenes exert dominant control over mitochondrial dynamics, oncogene-targeted therapies can be used to sensitize tumors to SMAC mimetics via their effects on fission/fusion dynamics. Collectively, these data demonstrate that perturbations to the mitochondrial dynamics network induce targetable vulnerabilities across diverse human tumors and, more broadly, suggest that the altered structures, activities, and trafficking of cellular organelles may facilitate additional cancer therapeutic opportunities.
In the decade since their advent, ablative fractional lasers have emerged as powerful tools to enhance drug delivery to and through the skin. Effective and highly customizable, laser-assisted drug ...delivery (LADD) has led to improved therapeutic outcomes for several medical indications. However, for LADD to reach maturity as a standard treatment technique, a greater appreciation of its underlying science is needed. This work aims to provide an in-depth guide to the technology's fundamental principles, experimental methodology and unique aspects of LADD data interpretation. We show that drug's physicochemical properties including solubility, molecular weight and tissue binding behavior, are crucial determinants of how laser channel morphology influences topical delivery. Furthermore, we identify strengths and limitations of experimental models and drug detection techniques, interrogating the usefulness of in vitro data in predicting LADD in vivo. By compiling insights from over 75 studies, we ultimately devise an approach for intelligent application of LADD, supporting its implementation in the clinical setting.
Display omitted
PDF
