Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Measurement of Jupiter's asymmetric gravity field.

The gravity harmonics of a fluid, rotating planet can be decomposed into static components arising from solid-body rotation and dynamic components arising from flows. In the absence of internal dynamics, the gravity field is axially and hemispherically symmetric and is dominated by even zonal gravity harmonics J2n that are approximately proportional to qn, where q is the ratio between centrifugal acceleration and gravity at the planet's equator. Any asymmetry in the gravity field is attributed to differential rotation and deep atmospheric flows. The odd harmonics, J3, J5, J7, J9 and higher, are a measure of the depth of the winds in the different zones of the atmosphere. Here we report measurements of Jupiter's gravity harmonics (both even and odd) through precise Doppler tracking of the Juno spacecraft in its polar orbit around Jupiter. We find a north-south asymmetry, which is a signature of atmospheric and interior flows. Analysis of the harmonics, described in two accompanying papers, provides the vertical profile of the winds and precise constraints for the depth of Jupiter's dynamical atmosphere.

Asteroid 21 Lutetia: low mass, high density.

Asteroid 21 Lutetia was approached by the Rosetta spacecraft on 10 July 2010. The additional Doppler shift of the spacecraft radio signals imposed by 21 Lutetia's gravitational perturbation on the flyby trajectory were used to determine the mass of the asteroid. Calibrating and correcting for all Doppler contributions not associated with Lutetia, a least-squares fit to the residual frequency observations from 4 hours before to 6 hours after closest approach yields a mass of (1.700 ± 0.017) × 10(18) kilograms. Using the volume model of Lutetia determined by the Rosetta Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) camera, the bulk density, an important parameter for clues to its composition and interior, is (3.4 ± 0.3) × 10(3) kilograms per cubic meter.

Randomised controlled trial of treatment of unilateral visual impairment detected at preschool vision screening.

OBJECTIVES: To test the efficacy of treatment for unilateral visual loss detected by preschool vision screening and the extent to which effectiveness varies with initial severity. DESIGN: Randomised controlled trial of full treatment with glasses and patching, if required, compared with glasses only or no treatment. Masked assessment of best corrected acuity after one year of follow up. SETTING: Eight UK eye departments. PARTICIPANTS: 177 children aged 3-5 years with mild to moderate unilateral impairment of acuity (6/9 to 6/36) detected by screening. RESULTS: Children in the full and glasses treatment groups had incrementally better visual acuity at follow up than children who received no treatment, but the mean treatment effect between full and no treatment was equivalent to only one line on a Snellen chart (0.11 log units; 95% confidence interval 0.050 to 0.171; P < 0.0001). The effects of treatment depended on initial acuity: full treatment showed a substantial effect in the moderate acuity group (6/36 to 6/18 at recruitment) and no significant effect in the mild acuity group (6/9 to 6/12 at recruitment) (P = 0.006 for linear regression interaction term). For 64 children with moderate acuity loss the treatment effect was 0.20 log units, equivalent to one to two lines on a Snellen chart. When all children had received treatment, six months after the end of the trial, there was no significant difference in acuity between the groups. CONCLUSIONS: Treatment is worth while in children with the poorest acuity, but in children with mild (6/9 to 6/12) unilateral acuity loss there was little benefit. Delay in treatment until the age of 5 did not seem to influence effectiveness.

Spurious genotypes in female nematodes resulting from contamination with male DNA.

Females of many invertebrates contain stored sperm or fertilized eggs or both, causing potential genotyping errors. We investigated errors caused by male DNA contamination by amplifying 5 microsatellites in DNA isolated from various tissue types in the nematode Ascaris lumbricoides. We observed additional alleles in 30/135 uterus-derived samples when compared with muscle controls, resulting in 20/135 (15%) incorrect genotypes and an underestimation of inbreeding. In contrast, we observed additional alleles in only 5/143 ovary-derived samples, resulting in 4/143 (3%) incorrect genotypes and no significant influence on inbreeding estimates. Because uterus constitutes approximately 17% of a female's organ weight, a substantial proportion of samples isolated from female tissue may contain male-derived DNA. Male contamination is easily avoided when using large nematodes such as A. lumbricoides. However, we urge caution for studies using DNA isolated from small invertebrates that store sperm or fertilized eggs or both.

Spontaneous access of proteins to buried nucleosomal DNA target sites occurs via a mechanism that is distinct from nucleosome translocation.

Intrinsic nucleosome dynamics termed "site exposure" provides spontaneous and cooperative access to buried regions of nucleosomal DNA in vitro. Two different mechanisms for site exposure have been proposed, one based on nucleosome translocation, the other on dynamic nucleosome conformational changes in which a stretch of the nucleosomal DNA is transiently released off the histone surface. Here we report on three experiments that distinguish between these mechanisms. One experiment investigates the effects on the accessibilities of restriction enzyme target sites inside nucleosomes when extra DNA (onto which the nucleosome may move at low energetic cost) is appended onto one end. The other two experiments test directly for nucleosome mobility under the conditions used to probe accessibility to restriction enzymes: one on a selected nonnatural nucleosome positioning sequence, the other on the well-studied 5S rRNA gene nucleosome positioning sequence. We find from all three assays that restriction enzymes gain access to sites throughout the entire length of the nucleosomal DNA without contribution from nucleosome translocation. We conclude that site exposure in nucleosomes in vitro occurs via a nucleosome conformational change that leads to transient release of a stretch of DNA from the histone surface, most likely involving progressive uncoiling from an end. Recapture at a distal site along DNA that has partially uncoiled would result in looped structures which are believed to contribute to RNA polymerase elongation and may contribute to spontaneous or ATP-driven nucleosome mobility. Transient open states may facilitate the initial entry of transcription factors and enzymes in vivo.

Poly(dA-dT) promoter elements increase the equilibrium accessibility of nucleosomal DNA target sites.

Polypurine tracts are important elements of eukaryotic promoters. They are believed to somehow destabilize chromatin, but the mechanism of their action is not known. We show that incorporating an A(16) element at an end of the nucleosomal DNA and further inward destabilizes histone-DNA interactions by 0.1 +/- 0.03 and 0.35 +/- 0.04 kcal mol(-1), respectively, and is accompanied by 1.5- +/- 0.1-fold and 1.7- +/- 0.1-fold increases in position-averaged equilibrium accessibility of nucleosomal DNA target sites. These effects are comparable in magnitude to effects of A(16) elements that correlate with transcription in vivo, suggesting that our system may capture most of their physiological role. These results point to two distinct but interrelated models for the mechanism of action of polypurine tract promoter elements in vivo. Given a nucleosome positioned over a promoter region, the presence of a polypurine tract in that nucleosome's DNA decreases the stability of the DNA wrapping, increasing the equilibrium accessibility of other DNA target sites buried inside that nucleosome. Alternatively (if nucleosomes are freely mobile), the presence of a polypurine tract provides a free energy bias for the nucleosome to move to alternative locations, thereby changing the equilibrium accessibilities of other nearby DNA target sites.

Patients with reconstruction of craniofacial or intraoral defects: development of instruments to measure quality of life.

Patients with reconstruction of craniofacial or intraoral defects experience a profound impact on their quality of life (QOL). This impact on QOL is influenced by the patients' medical conditions and the treatment interventions. Instruments to measure general QOL have been available for many years. A major criticism of QOL instruments is that too often the questions are not specific to the particular problems of a disease or condition. A search of the literature regarding QOL measurement for patients with maxillofacial implant-supported prostheses produced a short list of instruments, none of which were sufficiently developed or suited to the patients involved in reconstructive treatment. This study was designed to develop pretreatment and posttreatment questionnaires for measuring QOL for patients with reconstruction of a craniofacial defect and patients with reconstruction of loss of specific intraoral structures utilizing an implant-supported prosthesis (e.g., severe resorption of the maxilla or mandible or both). The goal was to develop brief, targeted instruments for this specific patient population. The produced instruments were sensitive and easy to administer and score, and no disruption of clinical care occurred with the administration of the questionnaires. The instruments were used with equal success both in face-to-face interviews and via mail.

Effects of histone acetylation on the equilibrium accessibility of nucleosomal DNA target sites.

Posttranslational acetylation of the conserved core histone N-terminal tail domains is linked to gene activation, but the molecular mechanisms involved are not known. In an earlier study we showed that removing the tail domains altogether by trypsin proteolysis (which leaves nucleosomes nevertheless intact) leads to 1.5 to 14-fold increases in the dynamic equilibrium accessibility of nucleosomal DNA target sites. These observations suggested that, by modestly increasing the equilibrium accessibility of buried DNA target sites, histone acetylation could result in an increased occupancy by regulatory proteins, ultimately increasing the probability of transcription initiation. Here, we extend these observations to a more natural system involving intact but hyperacetylated nucleosomes. We find that histone hyperacetylation leads to 1.1 to 1.8-fold increases in position-dependent equilibrium constants for exposure of nucleosomal DNA target sites, with an average increase of 1.4(+/-0.1)-fold. The mechanistic and biological implications of these results are discussed.

Sequence and position-dependence of the equilibrium accessibility of nucleosomal DNA target sites.

We have previously shown that nucleosomes are conformationally dynamic: DNA sequences that in the time-average are buried inside nucleosomes are nevertheless transiently accessible, even to large proteins (or any other macromolecule). We refer to this dynamic behavior as "site exposure". Here we show that: (i) the equilibrium constants describing this dynamic site exposure decrease progressively from either end of the nucleosomal DNA in toward the middle; and (ii) these position-dependent equilibrium constants are strongly dependent on the nucleosomal DNA sequence. The progressive decrease in equilibrium constant with distance inside the nucleosome supports the hypothesis that access to sites internal to a nucleosome is provided by progressive (transient) release of DNA from the octamer surface, starting from one end of the nucleosomal DNA. The dependence on genomic DNA sequence implies that a specific genomic DNA sequence could be a major determinant of target site occupancies achieved by regulatory proteins in vivo, by either governing the time-averaged accessibility for a given nucleosome position, or biasing the time-averaged positioning (of mobile nucleosomes), which in turn is a major determinant of site accessibility.

Need for evidence-based practice in prosthodontics.

STATEMENT OF PROBLEM: Patients, their insurers, the courts, and the scientific community are demanding more evidence to support the effectiveness of health care strategies. PURPOSE: This article describes evidence-based practice, its origins, and value as a way of addressing the demand for evidence of treatment effectiveness in maxillofacial prosthetics. MATERIAL AND METHODS: A limited review of maxillofacial prosthetics literature was performed using Medline over the years 1966 to 1998. The retrieved articles were classified by methodologic design and assessed for the strength of their evidence. RESULTS: Focused and speedy (but not necessarily comprehensive) literature searching methods are available. Critical appraisal skills are available and needed to assess the quality of evidence in support of a treatment and to maintain clinical skills. CONCLUSION: With appropriate skills and the availability of literature searching hardware and software, evidence-based practice is a powerful means for the practitioner to establish the effectiveness of individual patient treatment, and to prevent the diminution of clinical skills over the course of a career. These skills should be included in training programs.

Evaluation of Infection Processes and Resulting Disease Caused by Dendryphion penicillatum and Pleospora papaveracea on Papaver somniferum.

ABSTRACT Two pathogenic fungi of opium poppy, Pleospora papaveracea and Dendryphion penicillatum, were isolated from field material in Beltsville, MD. The processes of infection by these two fungi were studied to determine the optimal environmental conditions for infection. Both fungi formed appressoria capable of penetrating directly through the plant epidermal layer. Of the two fungi, P. papaveracea was more aggressive, causing more rapid necrosis. Appressorial formation by P. papaveracea occurred as early as 4 h after application of a conidial suspension to poppy leaves. P. papaveracea formed more appressoria than did D. penicillatum, especially at cool temperatures (7 to 13 degrees C). In greenhouse studies, P. papaveracea caused more damage to opium poppy than did D. penicillatum when applied in 10% unrefined corn oil. In the field, P. papaveracea was more consistent in its effects on opium poppy from a local seed source designated Indian Grocery. P. papaveracea caused higher disease ratings, more stem lesions, and equal or greater yield losses than did D. penicillatum on Indian Grocery. The late-maturing opium poppy variety White Cloud was severely damaged by disease, regardless of formulation or fungal treatment. P. papaveracea was the predominant fungus isolated from poppy seed capsules and the only fungus reisolated from the field the following year. These studies provide a better understanding of the infection process and the differences between these two pathogenic fungi and will be beneficial for the development of the fungi as biological control agents.

Nep1 Protein from Fusarium oxysporum Enhances Biological Control of Opium Poppy by Pleospora papaveracea.

ABSTRACT The fungus Pleospora papaveracea and Nep1, a phytotoxic protein from Fusarium oxysporum, were evaluated for their biocontrol potential on opium poppy (Papaver somniferum). Four treatments consisting of a control, P. papaveracea conidia, Nep1 (5 mug/ml), and P. papaveracea conidia plus Nep1 (5 mug/ml) were used in detached-leaf and whole-plant studies. Conidia of P. papaveracea remained viable for 38 days when stored at 20 or 4 degrees C. Nep1 was stable in the presence of conidia for 38 days when stored at 4 degrees C or for 28 days at 20 degrees C. The presence of Nep1 did not affect conidia germination or appressoria formation. Nep1 was recovered from drops applied to opium poppy leaves in greenhouse and field studies 24 h after treatment. Opium poppy treated with the combination of Nep1 and P. papaveracea had higher necrosis ratings than the other treatments. There were changes in the intercellular protein profiles, determined by sodium dodecyl sulfate gel electrophoresis and silver staining, due to application of treatments; the most intense occurred in response to the combination of Nep1 and P. papaveracea. The combination of Nep1 and P. papaveracea enhanced the damage caused to opium poppy more than either component alone.

Europa's differentiated internal structure: inferences from four Galileo encounters.

Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius. The thickness of Europa's outer shell of water ice-liquid must lie in the range of about 80 to 170 kilometers.