Correlation of transepidermal water loss with skin barrier properties in vitro: comparison of three evaporimeters

Aim: This study investigates the relationship between transepidermal water loss (TEWL) and skin permeability to tritiated water as a rapid assessment of the integrity of the barrier properties of skin as part of in vitro skin permeation studies.
Methods: TEWL values before and during the experimental period were measured using three evaporimeters (A, B, and C) representing different measuring principles and technologies. Single application of tritiated water was dosed on dermatomed human skin samples in a flow-through diffusion cell system. Radioactivity of the absorbed dose and the removable dose residues was counted to determine percent dose and flux rate. These data were further combined with TEWL values to analyze the correlation.
Results: Evaporimeter C, a closed chamber–condenser technology, had higher measurement capacity than other instruments, evaporimeter A, an open chamber, and evaporimeter B, a closed chamber ( P <0.001). The baseline TEWL value correlated with tritiated water flux ( r =0.34, P =0.04). The pattern of tritiated water expressed as percent dose permeated into receptor fluid was similar to that of TEWL values.
Conclusion: These data indicate that TEWL can be ascribed to be a measure of skin water barrier function. Further work should be conducted to interpret the significance of measuring TEWL by evaporimetry.     

Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

Background  

The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site.     

Position representations lag behind targets in multiple object tracking

In the multiple object tracking (MOT) task, observers can typically keep track of up to four moving objects. Little is known however about the extent to which object motion is used by observers during MOT. For example, direction and speed might be used to anticipate future positions. We here ask to what extent position reports lag behind targets or instead correspond to extrapolated positions. Using a range of different motion trajectory patterns, observers tracked 1-4 targets among distracters and reported the final position of one of the targets. On average, reports corresponded to previous positions rather than the final position. This lag varied across conditions from around 10 to 70 ms of the object’s trajectory. Although some have suggested that extrapolation occurs during MOT, we find no evidence of anticipation of future positions of targets. The significant increase in lag with speed of the object is consistent with slow or intermittent updating of object positions during tracking.     

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

A structural and functional model of bacterial nitric oxide reductase (NOR) has been designed by introducing two glutamates (Glu) and three histidines (His) in sperm whale myoglobin. X-ray structural data indicate that the three His and one Glu (V68E) residues bind iron, mimicking the putative Fe_B site in NOR, while the second Glu (I107E) interacts with a water molecule and forms a hydrogen bonding network in the designed protein. Unlike the first Glu (V68E), which lowered the heme reduction potential by ∼110 mV, the second Glu has little effect on the heme potential, suggesting that the negatively charged Glu has a different role in redox tuning. More importantly, introducing the second Glu resulted in a ∼100% increase in NOR activity, suggesting the importance of a hydrogen bonding network in facilitating proton delivery during NOR reactivity. In addition, EPR and X-ray structural studies indicate that the designed protein binds iron, copper, or zinc in the Fe_B site, each with different effects on the structures and NOR activities, suggesting that both redox activity and an intermediate five-coordinate heme-NO species are important for high NOR activity. The designed protein offers an excellent model for NOR and demonstrates the power of using designed proteins as a simpler and more well-defined system to address important chemical and biological issues.     

Geography and Travel Distance Impact Emergency Department Visits

Background: Little has been written about the geographic basis of emergency department (ED) visits. Objective: The objective of this study is to describe the impact of geography on ED visits. Methods: A retrospective analysis was conducted of ED visits during a 1-year period at a single institution using spatial interaction analysis that models the pattern of flow between a series of origins (census block groups) and a destination (ED). Patients were assigned to census block groups based upon their verified home address. The study hospital is the only Level I trauma, pediatric, and tertiary referral center in the area. There are 11 other hospitals with EDs within a 40-mile radius. Each patient visit within this radius, including repeat visits, was included. Patients with an invalid home address, a post office box address, or those who lived outside a 40-mile radius were excluded. ED visits per 100 population were calculated for each census block group. Results: There were 98,584 (95%) visits by 63,524 patients that met study inclusion criteria. Visit rates decreased with increasing distance from the ED (p < 0.0001). Nineteen percent of patients lived within 2 miles, 48% within 4 miles, and 92% within 12 miles of the ED. The Connecticut border, 7 miles south of the ED (p < 0.0001), the Connecticut River, 1 mile west of the ED (p < 0.0001), and the presence of a competing ED within 1 mile (p < 0.0001) negatively impacted block group ED visit rates. Travel distance was related to the percentage of visits that were high acuity (p < 0.0001), daytime (p < 0.01), or resulted in admission (p < 0.0001). Conclusions: Geography and travel distance significantly impact ED visits.     

Exploring the Feasibility of Dose Escalation Positron Emission Tomography–Positive Disease with Intensity-Modulated Radiation Therapy and the Effects on Normal Tissue Structures for Thoracic Malignancies

The pattern of failure is one of the major causes of mortality among thoracic patients. Studies have shown a correlation between local control and dose. Intensity-modulated radiation therapy (IMRT) has resulted in conformal dose distributions while limiting dose to normal tissue. However, thoracic malignancies treated with IMRT to highly conformal doses up to 70 Gy still have been found to fail. Thus, the need for dose escalation through simultaneous integrated boost (SIB) may prove effective in minimizing reoccurrences. For our study, 28 thoracic IMRT plans were reoptimized via dose escalation to the gross tumor volume (GTV) and planning target volume (PTV) of 79.2 Gy and 68.4 Gy, respectively. Reoccurrences in surrounding regions of microscopic disease are rare therefore, dose-escalating regional nodes (outside GTV) were not included. Hence, the need to edit GTV margins was acceptable for our retrospective study. A median dose escalation of approximately 15 Gy (64.8–79.2 Gy) via IMRT using SIB was deemed achievable with minimal percent differences received by critical structures compared with the original treatment plan. The target's mean doses were significantly increased based on p-value analysis, while the normal tissue structures were not significantly changed.     

Mapping the human face: biophysical properties

Background: Facial skin exhibits unique biophysical properties that are distinct from skin belonging to other areas of the body. Small to large regional differences in biophysical properties between facial sites are observed. Technological advances in dermatological research allow a quantitative study of the biophysical qualities of the face and its relation to skin elsewhere. However, comprehensive studies examining inter‐regional variations using each of the six standard biophysical parameters have been few. We summarize findings on the biophysical parameters used to explore the human face as well as regional differences in skin reactivity to chemical irritants. Methods: We performed a literature search using Pubmed, Embase, Science Citations Index, and the UCSF's dermatological library on biophysical parameters and skin physiology pertaining to the human face. Results: Distinct regional differences in transepidermal water loss (TEWL), capacitance, blood flow, sebum, pH, and temperature were demonstrated in facial skin. However, studies cannot be compared with each other because each uses different anatomical sites, skin conditions, and measurement techniques. Intraregional differences in TEWL, sebum, and temperatures were observed on the cheeks and appeared to follow characteristic distribution patterns. Higher blood flow levels and skin temperatures were generally observed in areas with dense networks of blood vessels such as the nose and perioral region. Areas such as the forehead, nose, and chin consistently showed higher sebum casual levels, but variability in sebum levels between sites was also observed. The susceptibility of the face to hexyl nicotinate, sodium lauryl sulfate, and benzoic acid differed depending on location and age. Conclusion: Establishing a standardized biophysical profile of the human face will help to improve therapeutics, and further our understanding of differences in chemical reactivity and disease distribution. Future research necessitates standardization of the anatomical sites studied, sample size, and experimental protocols.