Effect of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a high-sugar meal breakfast the following day in postmenopausal women: a randomized cross-over study.

High-sugar consumption is related to dyslipidemia. How acute exercise affects postprandial lipid and lipoprotein particle responses to a high-sugar meal (HSM) in postmenopausal women is unclear. We examined the effects of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a HSM breakfast the following day in 22 postmenopausal women. Subjects underwent exercise (EX) and no exercise (NE) conditions in the evening 13-16 h before the HSM breakfast consumption, in a random order. During the EX condition, subjects performed supervised aerobic exercise for 60 min at 75% of age-predicted maximum heart rate. The HSM (75.6% carbohydrate and 33% energy needs) was consumed after a 12-h fast. Serum lipids and lipoproteins were assessed at baseline and postprandially (60, 120, 180 min). Repeated measures analysis showed significantly lower area under the curve (geometric means [95% CI]) for triglycerides (TG) (2.96[2.43, 3.61] vs. 3.24[2.70, 3.88] mmol/L*hr; p = 0.049) and very low density lipoprotein particles (VLDLP) (114.6[88.2, 148.9] vs. 134.3[108.1, 166.9] nmol/L*hr; p = 0.02) during the EX versus NE condition. There were no condition effects for other variables. In conclusion, the EX versus NE condition lowered postprandial AUC for TG and VLDLP following HSM consumption in postmenopausal women.Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.

Pharmacogenomics and Psychiatric Nursing.

The treatment of mental illness is often done on a trial-and-error basis and achieving therapeutic benefits from a medication is not always guaranteed. Pharmacogenomics explores the role of gene-gene interactions and interindividual responses to a drug and may be promising in the guidance of pharmacotherapeutic options. In the present study, the impact of pharmacogenomic testing in management of mental health medication was investigated. Participants were identified at a local outpatient mental health facility through convenience sampling. Retrospective chart review included medication history, adverse drug reactions, pharmacogenomic history, and demographic data including insurance coverage. Chart review focused on six months pre- and post-pharmacogenomic for a comparison with the patient serving as their own control. Results indicate a high incidence of alterations in two specific cytochrome enzymes, CYP2D6 and CYP2C19. In total, 82% of the sample had variations with CYP2D6, while 64% of individuals had variations with CYP2C19. In total, 91% of patients tested received Medicaid or Medicare. Post-pharmacogenomic testing, all patient drug regimens were modified, and all reported less adverse side effects. Moreover, advanced practice nurse providers educated patients about the availability of genetic testing, initiated testing and provided care based on findings. These results demonstrate the utility of genetic testing in the realm of mental health. Future directions involve further exploring the benefits of pharmacogenomic testing in this vulnerable population.

Pharmacogenomics and Implications for Nursing Practice.

PURPOSE: This article aims to introduce the nurse to pharmacogenomics and its implications for clinical practice with regard to drug therapy. ORGANIZING CONSTRUCTS: Pharmacogenomics is discussed with regard to the basic tenets, relationships to common health conditions, education and practice resources, and implications for nursing practice. METHODS: Peer-reviewed literature, websites, and expert professional guidelines were reviewed with relation to pharmacogenomics and nursing practice. FINDINGS: The genetic-genomic literature has grown significantly since the completion of the Human Genome Project in 2003. This information is now being translated into practice with regard to the patient's genetic profile and the impact on drug therapy, which is pharmacogenomics. CONCLUSIONS: The utilization of the patient genetic-genomic profile is beginning to have an impact on patient drug therapy in clinical practice. CLINICAL RELEVANCE: Nurses are in the position to make sure, with the increased translation of pharmacogenomics into clinical practice, that adverse drug reactions are avoided and doses are optimized.

Worldwide experience with sugammadex sodium: implications for the United States.

Sugammadex sodium is a modified γ-cyclodextrin with a very high affinity for rocuronium and, to a lesser extent, vecuronium molecules. In vivo administration results in immediate encapsulation of rocuronium and vecuronium, resulting in termination of neuro- muscular blockade, usually within 3 minutes. This new neuromuscular blocking agent is specific for the aminosteroidal neuromuscular blocking agents rocuronium and vecuronium. Experience gained through worldwide clinical use of sugammadex offers US anesthesia providers the opportunity to better understand this new drug and its clinical applications. The seminal and current literature concerning clinical use of sugammadex is reviewed, and considerations for its incorporation into practice are provided.

Psychiatric mental health nurse practitioner student knowledge and perceptions of pharmacogenetic testing.

Psychotropic medications are typically prescribed in a trial-and-error fashion, and some providers are beginning to utilize pharmacogenetic testing (PGx) as a supplemental prescribing tool in treatment decision making. PGx testing shows potential in enhancing provider insights into personalized prescribing for patients by examining genetic information related to drug metabolism. Literature points to providers' lack of knowledge in PGx interpretation as a main barrier, including psychiatric mental health nurse practitioners (PMHNPs). The aim of this study was to measure a difference, if any, in the knowledge and perceptions of PGx after implementation using a pre-post design. This study implemented an educational intervention on graduate nursing students (n = 15). Data were collected by using a pre- and post-interventional questionnaire. Results demonstrated a significant difference in findings related to students' knowledge (p < 0.001), students' skills related to pharmacogenetics, (p < 0.001), as well as students' perceived ability to implement pharmacogenetics into their practice, (p = 0.028). The authors propose that the knowledge gained from the study demonstrates the importance of introducing PGx education into the PMHNP curricula and to prepare future PMHNPs to confidently utilize PGx in their clinical practice.

Short Communication: Stellate Ganglion Blockade for Persistent Olfactory and Gustatory Symptoms Post-COVID-19.

One hundred ninety-five patients presenting with post-COVID symptomology, including parosmia and dysgeusia, underwent reversible stellate ganglion blockade. Stellate ganglion blockade was performed at an outpatient facility, and patients were evaluated via survey at seven days post-injection. Of the 195 participants, ages ranged from 18-69 years of age with the breakdown of sexes being females n = 157 and males n = 38. The most significant finding was a reported improvement in olfaction post-injection in 87.4% of subjects. The effectiveness of this novel treatment for post-COVID is promising and warrants further investigation.

Effects of Interfraction Dose Variations of Target and Organs at Risk on Clinical Outcomes in High Dose Rate Brachytherapy for Cervical Cancer.

Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose and probability of risk-free local control (RFLC) were calculated using the utility model. The IDVs were well-fitted by the left-skewed Beta distribution, which caused a 3.99% decrease in local control probability and a 1.80% increase in treatment failure. Utility with respect to IDV uncertainty increased the RFLC probability by 6.70% and predicted an optimal dose range of 83 Gy-91 Gy EQD2. It was also found that a 10 Gy dose escalation would not affect toxicity. In conclusion, HRCTV IDV uncertainty reduced LC probabilities and increased treatment failure rates. A dose escalation may help mitigate such effects.

Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy.

BACKGROUND: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. METHODS: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous 19F nanoemulsion injection, followed by a baseline 19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and 9F signal using MRI. RESULTS: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. CONCLUSION: These results demonstrate the potential of 19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.

Patient-specific dose correction for prostate postimplant evaluation with flexible timing of postimplant imaging.

PURPOSE: The dosimetric effect of edema on prostate implants have long been realized, but large uncertainties still exist in the estimation of dose actually received by the prostate. This study attempted to develop a new method to accurately estimate dose delivered to the prostate accounting for the variation of prostate volume and seed distribution, edema half-lives, and times for postimplant evaluation. METHODS AND MATERIALS: A series of prostate seed implants for Cs-131, Pd-103, and I-125 with various prostate volumes were simulated in a water phantom using the TG-43 algorithm on the Varian Eclipse treatment planning system. Dose analysis was performed to derive a quantitative relationship between the prostate peripheral dose and the prostate radius with the variation of prostate volume and seed distribution. Using this relationship to calculate dynamically, the total dose accumulated in the prostate (DT ) accounting for the variation of prostate volume and seed distribution and edema half-lives. Moreover, the total dose can be estimated statically based on the prostate volume that can be determined in a computerized tomography (CT) image taken at a time after implantation. The statically estimated total dose (DCT ) was compared with DT to determine optimal imaging times as well as dose correction factors for other imaging times. RESULTS: An inverse power law was established between the prostate peripheral dose and prostate radius. The value of the power was 1.3 for Cs-131 and I-125, and 1.5 for Pd-103, respectively. DT was derived dynamically using the inverse power law. Given the edema half-lives, TE , of 4, 9.3, and 25 days and the volume expansion of 1.1 and 2.0 times of the prostate without edema, the optimal times for postimplant imaging were: 7, 9, and 16 days for TE  = 4 days; 10, 14, and 28 days for TE  = 9.3 days; and 12, 19, 45 days TE  = 25 days, for Cs-131, Pd-103, and I-125, respectively. DCT calculated using the prostate volume determined on the optimal days agreed with DT to 0.0%-1.8% and within 0.3% for most cases. For various prostate volumes, edema half-lives, and nonoptimal times, DCT was able to achieve a 1% accuracy. CONCLUSION: The postimplant dose calculation based on the proposed inverse power law for prostate seed implants with edema has improved the accuracy of postimplant dosimetry with accurate and patient-specific dose corrections accounting for prostate size, edema half-life, and postimplant imaging times. Optimal times for postimplant imaging have been accurately determined, and the high accuracy of postimplant dose calculation can be achieved for both optimal imaging times and nonoptimal imaging times.

Statistical Analysis of Interfraction Dose Variations of High-Risk Clinical Target Volume and Organs at Risk for Cervical Cancer High-Dose-Rate Brachytherapy.

Purpose: High-dose-rate (HDR) brachytherapy for cervical cancer treatment includes significant uncertainties. The aim of this study was to quantify the interfraction dosimetric variation (IDV) of the high-risk clinical target volume (HRCTV) from the prescribed dose and the corresponding effect on organ-at-risk (OAR) dose based on a comprehensive statistical analysis. Methods and Materials: Fifty patients with cervical cancer treated with high-dose-rate intracavity brachytherapy from October 2019 to December 2020 were retrospectively analyzed. The OARs of interest were the rectum, bladder, sigmoid, and bowel. The dosimetric parameters evaluated for all patients was the dose absorbed by 90% of the HRCTV ( D 90 ) and the dose absorbed by 0.1 ( D 0.1 c c ) and 2 cm3 ( D 2 c c ) of each respective OAR. The HRCTV variations were from the prescribed dose and the OAR variations were from the corresponding tolerance dose. Distribution fitting of the HRCTV variations was determined to quantify the IDV. Comparative statistics of the HRCTV variations with the OAR variations were conducted to determine correlations. Results: The mean HRCTV variation from the prescribed dose was -2.53% ± 8.74%. The HRCTV variations and OAR variations showed moderate to weak linear correlations despite the variations being relative to each other, with the bladder D 2 c c having the strongest correlation. There was a 30.0% (±2.62%, 95% confidence interval) probability of underdosing the HRCTV (-5% variation from prescription) and a 23.3% (±2.62%, 95% confidence interval) probability of overdosing the HRCTV (+5% variation from prescription). This tendency to underdose the HRCTV was a consequence of HRCTV IDV not being normally distributed. Conclusions: HRCTV dosimetric variations and OAR variations were complexly correlated with the bladder D 2 c c having the strongest correlation. HRCTV IDV was best described as a left-skewed distribution that indicates a tendency of underdosing the HRCTV. The clinical significance of such dose variations is expected and will be further investigated.

The effects of high-fidelity simulation on salivary cortisol levels in SRNA students: a pilot study.

The use of clinical simulation in graduate level nursing education provides the opportunity for students to learn and apply theoretical practices of nursing care in a safe and controlled environment. It was postulated that laboratory simulation would mimic the stress levels of a real clinical situation as measured by the stress hormone cortisol. The purpose of this study was to determine whether high-fidelity simulation approximates the stress experienced by nurse anesthesia students in the operating room. Participants (n = 21) were recruited from an accredited nurse anesthesia program in the southern U.S. Saliva was collected for 3 days under controlled conditions for baseline data. Next, saliva was collected for 3 days: the day before, the day of, and the day after simulation. The same process was repeated for the first clinical day in the operating room. The participants acted as their own control. There was a significant (p < 0.05) increase in cortisol levels during laboratory simulation as compared to baseline values. Although levels of cortisol were higher during clinical time than baseline, this increase was not significant (p > 0.05), and levels were lower than levels during simulation. Laboratory simulation of patient scenarios raised the stress hormone cortisol level threefold above baseline levels in nurse anesthesia students, while actual clinical experience did not.

Sex differences in the impact of childhood socioeconomic status on immune function.

Early life stress increases one's risk for health problems later in life, and many studies find that these effects are sex-differentiated. Here, we examined relationships between multiple sources of early life stress and adult immune function in humans across several functional assays. Adult participants provided retrospective information about their childhood (a) socioeconomic status, (b) household unpredictability, and (c) exposure to adverse experiences. Participants' peripheral blood mononuclear cells (PBMCs) were then isolated for use in functional assays of immune performance: (a) tumor cell lysis by natural killer cells, (b) phagocytosis of Escherichia coli bioparticles, and (c) mitogen-induced leukocyte proliferation and cytokine release. In men, lower childhood socioeconomic status predicted decrements in immunological performance across functional assays, along with greater spontaneous cytokine release from PBMCs. These changes co-occurred with elevations in plasma testosterone levels. Similar effects were not observed for other sources of stress, nor were they found in women (with the exception of spontaneous cytokine release). These findings provide evidence that low childhood socioeconomic status has a lasting negative impact on multiple aspects of immune function, particularly in men.

Radiation-induced oral mucositis hamster model using a linear accelerator enhances clinical relevance of preclinical studies for treatment strategy investigation.

Translational animal models for oral mucositis (OM) are necessary to simulate and assess the bioclinical effects and response in humans. These models should simulate high levels of radiation exposure that leads to oxidative stress and inflammatory-initiated tissue changes. Hamster models have been extensively studied to observe pathological effects of radiation exposure and help in the development of effective treatments. To successfully evaluate the potential for treatment regimens with consistency and relevance, a radiation-induced OM hamster model was developed using a clinical linear accelerator utilized by cancer patients daily. The dose exposure to the isolated, everted cheek pouch of a hamster, as well as the progression of injury, pro-inflammatory marker, histological, and elasticity analyses of the buccal pouch were conducted to verify replicability and reproducibility of the injury model. The findings from this model demonstrated its ability to consistently induce injury and resolution over 28 days using an acute dose of 60 Gy. This model was developed to enhance clinical relevance when evaluating potential efficacious treatments and can now be utilized in efficacy studies to better evaluate developed therapeutics in a preclinical model that is easy to translate to clinical studies..

Independent calculation of dose from a helical TomoTherapy unit.

A new calculation algorithm has been developed for independently verifying doses calculated by the TomoTherapy Hi.Art treatment planning system (TPS). The algorithm is designed to confirm the dose to a point in a high dose, low dose-gradient region. Patient data used by the algorithm include the radiological depth to the point for each projection angle and the treatment sinogram file controlling the leaf opening time for each projection. The algorithm uses common dosimetric functions [tissue phantom ratio (TPR) and output factor (Scp)] for the central axis combined with lateral and longitudinal beam profile data to quantify the off-axis dose dependence. Machine data for the dosimetric functions were measured on the Hi.Art machine and simulated using the TPS. Point dose calculations were made for several test phantoms and for 97 patient treatment plans using the simulated machine data. Comparisons with TPS-predicted point doses for the phantom treatment plans demonstrated agreement within 2% for both on-axis and off-axis planning target volumes (PTVs). Comparisons with TPS-predicted point doses for the patient treatment plans also showed good agreement. For calculations at sites other than lung and superficial PTVs, agreement between the calculations was within 2% for 94% of the patient calculations (64 of 68). Calculations within lung and superficial PTVs overestimated the dose by an average of 3.1% (sigma=2.4%) and 3.2% (sigma=2.2%), respectively. Systematic errors within lung are probably due to the weakness of the algorithm in correcting for missing tissue and/or tissue density heterogeneities. Errors encountered within superficial PTVs probably result from the algorithm overestimating the scatter dose within the patient. Our results demonstrate that for the majority of cases, the algorithm could be used without further refinement to independently verify patient treatment plans.

An update on sugammadex sodium.

Sugammadex sodium is the generic drug name for the novel modified gamma cyclodextrin that terminates neuromuscular blockade induced by aminosteroidal neuromuscular blocking agents. Published phase II and phase III clinical data support preclinical and clinical phase I study findings of fast, safe, and efficacious reversal of all levels of neuromuscular blockade induced by rocuronium and vecuronium. Low levels of neuromuscular blockade induced by pancuronium have also been successfully reversed by sugammadex. This agent does not reverse the bis-isoquinoline neuromuscular blocking agents. Special patient populations, including pediatric, elderly, cardiac, and renal-compromised subjects, have been studied in phase III. This update focuses on the most recent findings of phase II and III clinical studies.

Unlocking the secrets of 2 common cardiac conditions.

Find out about the latest guidelines for unstable angina and non-ST-segment-elevation myocardial infarction.

Algorithmic determination of source orientations for the CivaSheet directional brachytherapy device.

PURPOSE: The CivaSheet device uses multiple directionally shielded Pd-103 CivaDot sources to produce a directional planar dose distribution. In postplanning, manually digitizing the 3D source orientation is challenging because the 3D vector must be digitized by using 2D displayed images. The aim of this study is to develop an algorithm that will automatically determine the direction of each CivaDot source based on the location of sources adjacent to it. METHODS AND MATERIALS: The algorithm determines the source direction by averaging the normal directions of multiple local planes established by the adjacent sources. The algorithm was tested on a manually constructed CivaSheet-like device that was CT scanned in known flat geometries and two known curved geometries. Algorithmically determined source directions were compared with the known directions. The algorithm was also used on a postplan for a gynecological pelvic sidewall tumor bed implant and compared against manual digitization of the source directions. RESULTS: For the flat and curved test geometries, the average angular difference between the algorithm determined and known orientation was 1.2° ± 0.8° (flat geometry), 1.7° ± 2.1° (curve about vertical axis), and 2.3° ± 2.4° (curve about horizontal axis). For the patient case, results showed on average a 23.1° ± 10.8° difference between the manual digitized orientation and the algorithm's predicted orientation. CONCLUSIONS: The algorithm calculates the source orientation with accuracy better than 2.3° for the controlled experiments. In addition to its accuracy, the algorithm produces consistent results and lessens the difficult challenge of orienting the partially shielded sources.

Effect of acute exercise on postprandial endothelial function in postmenopausal women: a randomized cross-over study.

High-sugar intake may cause endothelial dysfunction. It is unknown if a bout of aerobic exercise improves endothelial dysfunction caused by a high-sugar meal in postmenopausal women. This study evaluated if prior aerobic exercise attenuates postprandial endothelial dysfunction in postmenopausal women. Twenty-two postmenopausal women (age [mean±SD]: 60.4±6.5 years; % body fat: 40.3%±7.5%) underwent an exercise (EX) or no exercise (NE) condition, in a random order, 13-16 hours prior to the high-sugar meal consumption. The EX condition included a 60 min bout of supervised aerobic exercise at 75% of age-predicted maximum heart rate. The high-sugar meal, consumed after a 12-hour fast, contained 33% of the subjects' daily energy needs, and 75.6% energy from carbohydrates. Flow-mediated dilation (FMD) and blood concentrations of glucose, insulin, endothelin-1 (ET-1), and nitric oxide (NO) were assessed at baseline and 60 min, 120 min, and 180 min postprandially. Repeated measures analysis test showed that there were no condition by time interaction or condition effects for FMD, glucose, insulin, or NO. There was a significant condition by time interaction but no condition effect for ET-1. Area under the curve was also not different by condition for insulin sensitivity or the above variables. In conclusion, prior aerobic exercise compared with NE did not affect FMD, blood glucose, insulin, ET-1 or NO concentrations, or insulin sensitivity following a high-sugar meal in postmenopausal women. Future studies should look at the effect of different EX intensities on meal-induced endothelial dysfunction in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.