Radiotherapy (RT) is commonly used in the treatment of breast cancer and often, despite advances in fractionated dosing schedules, produces undesirable skin toxicity. The purpose of this study was to ...evaluate the feasibility of using a keratin-based topical cream, KeraStat® Cream (KC; KeraNetics, Inc., Winston Salem, NC, USA) to manage the symptoms of radiation dermatitis (RD) in breast cancer patients undergoing RT.
A total of 24 subjects were enrolled on this single-center, randomized, open-label study. Participants were randomly assigned to KC or standard of care (SOC, patient's choice of a variety of readily available creams or moisturizers). Patients were asked to apply the assigned treatment to the irradiated area twice daily, beginning with day 1 of RT, through 30 days post-RT. The primary outcome was compliance of use. Secondary outcomes included safety and tolerability of KC, as well as RD severity assessed using the Radiation Therapy Oncology Group (RTOG) scale and the patient-reported Dermatology Life Quality Index (DLQI).
All subjects in the KC group were assessed as compliant with no adverse events. The rate of RTOG Grade 2 RD was lower in the KC group (30.8%) compared to the SOC group (54.5%,
= .408). At the final RT visit, the mean RTOG RD score was lower in the KC group (1.0) versus the SOC group (1.4). Similarly, patient-reported quality of life measured by the DLQI at the end of RT was improved in the KC group (mean 4.25, small effect) versus the SOC group (mean 6.18, moderate effect,
= .412).
KC was safe and well tolerated with no adverse events. Though efficacy measures were not powered to draw definitive conclusions, trends and clinical assessments suggest that there is a benefit of using KC compared to SOC for breast cancer patients treated with RT, and a larger powered study for efficacy is warranted.
This clinical trial is registered as NCT03374995 titled KeraStat(R) Cream for Radiation Dermatitis.
We present phase resolved optical spectroscopy and photometry of V4580 Sagittarii, the optical counterpart to the accretion powered millisecond pulsar SAX J1808.4−3658, obtained during the 2008 ...September/October outburst. Doppler tomography of the N iiiλ4640.64 Bowen blend emission line reveals a focused spot of emission at a location consistent with the secondary star. The velocity of this emission occurs at 324 ± 15 km s−1; applying a ‘K-correction’, we find the velocity of the secondary star projected on to the line of sight to be 370 ± 40 km s−1. Based on existing pulse timing measurements, this constrains the mass ratio of the system to be 0.044+0.005−0.004, and the mass function for the pulsar to be 0.44+0.16−0.13 M⊙. Combining this mass function with various inclination estimates from other authors, we find no evidence to suggest that the neutron star in SAX J1808.4−3658 is more massive than the canonical value of 1.4 M⊙. Our optical light curves exhibit a possible superhump modulation, expected for a system with such a low mass ratio. The equivalent width of the Ca ii H and K interstellar absorption lines suggest that the distance to the source is ∼2.5 kpc. This is consistent with previous distance estimates based on type-I X-ray bursts which assume cosmic abundances of hydrogen, but lower than more recent estimates which assume helium-rich bursts.
Abstract Objective To assess the health literacy and numeracy skills of Spanish-speaking parents of young children and to validate a new Spanish language health literacy assessment for parents, the ...Spanish Parental Health Literacy Activities Test (PHLAT Spanish). Methods Cross-sectional study of Spanish-speaking caregivers of young children (<30 months) enrolled at primary care clinics in 4 academic medical centers. Caregivers were administered the 10-item PHLAT in addition to validated tests of health literacy (S-TOFHLA) and numeracy (WRAT-3 Arithmetic). Psychometric analysis was used to examine item characteristics of the PHLAT-10 Spanish, to assess its correlation with sociodemographics and performance on literacy/numeracy assessments, and to generate a shorter 8-item scale (PHLAT-8). Results Of 176 caregivers, 77% had adequate health literacy (S-TOFHLA), whereas only 0.6% had 9th grade or greater numeracy skills. Mean PHLAT-10 score was 41.6% (SD 21.1). Fewer than one-half (45.5%) were able to read a liquid antibiotic prescription label and demonstrate how much medication to administer within an oral syringe. Less than one-third (31.8%) were able to interpret a food label to determine whether it met WIC (Special supplemental nutrition program for Women, Infants, and Children) guidelines. Greater PHLAT-10 score was associated with greater years of education (r = 0.49), S-TOFHLA (r = 0.53), and WRAT-3 (r = 0.55) scores ( P < .001). Internal reliability was good (Kuder-Richardson coefficient of reliability; KR-20 = 0.61). An 8-item scale was highly correlated with the full 10-item scale (r = 0.97, P < .001), with comparable internal reliability (KR-20 = 0.64). Conclusions Many Spanish-speaking parents have difficulty performing health-related literacy and numeracy tasks. The Spanish PHLAT demonstrates good psychometric characteristics and may be useful for identifying parents who would benefit from receiving low-literacy child health information.
Abstract Background Implant infections in the setting of breast reconstruction present a significant setback for breast cancer patients. Traditional management of implant infections is predicated on ...operative removal of the implant and delayed replacement. Another option for implant infection management has emerged in which the soft tissue infection is neutralized, the implant is removed and the surgical site washed out, and a new implant replaced immediately. Here we present our findings with the implementation of this technique and an algorithm for choosing which patients are the most appropriate candidates based on retrospective review. Methods A retrospective chart review was performed at the University of Michigan of patients who underwent operative removal of infected expanders from January 1, 2010 to December 31, 2015 by the senior authors. Final reconstructive outcome, time to reconstruction, and infection recurrence were evaluated. Results A total of twenty patients with clinical signs of implant infections were identified. Sixteen of twenty patients with clinical signs of implant infection underwent immediate implant exchange. Fifteen patients remained infection-free, while one patient developed recurrent infection within one month, which was treated with device removal. Mean time to final reconstruction in the 15 patients who remained infection-free was 207 days while the four patients who underwent removal without immediate replacement had a 75% rate of non-completion at over 500 days. Conclusions Our findings demonstrate that immediate implant exchange safely offers patients the opportunity to remain on a path towards reconstruction. These findings offer support for a paradigm shift in our management of implant infections in breast reconstruction patients who already face challenges associated with breast cancer care.
Objective Obesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of ...hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. Study Design Zucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro. Results Streptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner. Conclusion These findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women.
ABSTRACT
IGR J17062–6143 is an ultracompact X-ray binary (UCXB) with an orbital period of 37.96 min. It harbours a millisecond X-ray pulsar that is spinning at 163 Hz and and has continuously been ...accreting from its companion star since 2006. Determining the composition of the accreted matter in UCXBs is of high interest for studies of binary evolution and thermonuclear burning on the surface of neutron stars. Here, we present a multiwavelength study of IGR J17062–6143 aimed to determine the detailed properties of its accretion disc and companion star. The multi-epoch photometric UV to near-infrared spectral energy distribution (SED) is consistent with an accretion disc Fν ∝ ν1/3. The SED modelling of the accretion disc allowed us to estimate an outer disc radius of $R_{\rm out} = 2.2^{+0.9}_{-0.4} \times 10^{10}$ cm and a mass-transfer rate of $\dot{m} = 1.8^{+1.8}_{-0.5}\times 10^{-10}$ M⊙ yr−1. Comparing this with the estimated mass-accretion rate inferred from its X-ray emission suggests that ≳90 per cent of the transferred mass is lost from the system. Moreover, our SED modelling shows that the thermal emission component seen in the X-ray spectrum is highly unlikely from the accretion disc and must therefore represent emission from the surface of the neutron star. Our low-resolution optical spectrum revealed a blue continuum and no emission lines, i.e. lacking H and He features. Based on the current data we cannot conclusively identify the nature of the companion star, but we make recommendations for future study that can distinguish between the different possible evolution histories of this X-ray binary. Finally, we demonstrate how multiwavelength observations can be effectively used to find more UCXBs among the LMXBs.
Abstract
We present timing and spectral analysis of a sample of seven hard X-ray selected cataclysmic variable candidates based on simultaneous X-ray and optical observations collected with ...XMM–Newton, complemented with Swift/BAT and INTEGRAL /IBIS hard X-ray data and ground-based optical photometry. For six sources, X-ray pulsations are detected for the first time in the range of ∼296–6098 s, identifying them as members of the magnetic class. Swift J0927.7−6945, Swift J0958.0−4208, Swift J1701.3−4304, Swift J2113.5+5422 and possibly PBC J0801.2−4625 are intermediate polars (IPs), while Swift J0706.8+0325 is a short (1.7 h) orbital period polar, the 11th hard X-ray-selected identified so far. X-ray orbital modulation is also observed in Swift J0927.7−6945 (5.2 h) and Swift J2113.5+5422 (4.1 h). Swift J1701.3−4304 is discovered as the longest orbital period (12.8 h) deep eclipsing IP. The spectra of the magnetic systems reveal optically thin multitemperature emission between 0.2 and 60 keV. Energy-dependent spin pulses and the orbital modulation in Swift J0927.7−6945 and Swift J2113.5+5422 are due to intervening local high-density absorbing material (N
H ∼ 1022 − 23 cm−2). In Swift J0958.0−4208 and Swift J1701.3−4304, a soft X-ray blackbody (kT ∼ 50 and ∼80 eV) is detected, adding them to the growing group of ‘soft’ IPs. White dwarf masses are determined in the range of ∼ 0.58–1.18 M⊙, indicating massive accreting primaries in five of them. Most sources accrete at rates lower than the expected secular value for their orbital period. Formerly proposed as a long-period (9.4 h) nova-like CV, Swift J0746.3−1608 shows peculiar spectrum and light curves suggesting either an atypical low-luminosity CV or a low-mass X-ray binary.
Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin ...(ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance. Here, we evaluate the in vitro drug sensitivity profile of normally-developing P. falciparum ring stages and DHA-pretreated dormant rings (DP-rings) using a panel of antimalarial drugs, including the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. We report that while KDU691 shows no activity against rings, it is highly inhibitory against DP-rings; a drug effect opposite to that of ART. Moreover, we provide evidence that KDU691 also kills DP-rings of P. falciparum ART-resistant strains expressing mutant K13.
Abstract
We present rapid, multiwavelength photometry of the low-mass X-ray binary Swift J1357.2-0933 during its 2017 outburst. Using several sets of quasi-simultaneous ULTRACAM/NTT (optical), NuSTAR ...(X-ray), XRT/Swift (X-ray), SALT (optical), and ATCA (radio) observations taken during outburst decline, we confirm the frequent optical dipping that has previously been noted both in outburst and in quiescence. We also find: (1) that the dip frequency decreases as the outburst decays, similar to what was seen in the previous outburst, (2) that the dips produce a shape similar to that in binary systems with partial disc occultations, (3) that the source becomes significantly bluer during these dips, indicating an unusual geometry compared to other LMXB dippers, and (4) that dip superposition analysis confirms the lack of an X-ray response to the optical dips. These very unusual properties appear to be unique to Swift J1357.2−0933, and are likely the result of a high binary inclination, as inferred from features such as its very low outburst X-ray luminosity. From this analysis as well as X-ray/optical timing correlations, we suggest a model with multicomponent emission/absorption features with differing colours. This could include the possible presence of a sporadically occulted jet base and a recessed disc. This source still hosts many puzzling features, with consequences for the very faint X-ray transients population.
Abstract Background Whereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with ...preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample. Methods and Results Medical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis–St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF. Conclusions Incidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.
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