Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

COVID-19 Vaccine Uptake Among Students in Public Institutions of Higher Education in Arkansas in 2021.

OBJECTIVE: Disparities in COVID-19 vaccine coverage among college students are not well studied. We analyzed the extent of COVID-19 vaccination among all students at public institutions of higher education in Arkansas in spring and fall 2021 and examined factors associated with vaccination rates. METHODS: We matched student enrollment data for the spring and fall 2021 semesters separately with immunization registry data to determine the COVID-19 vaccination status of students in each semester. We used multivariable logistic regression to determine variables associated with being fully vaccinated. RESULTS: Overall, by the end of the fall 2021 semester, 49.1% of students were fully vaccinated, compared with 52.3% of students at the end of the spring 2021 semester. However, we observed important differences between student groups. Students who were in rural areas (vs urban areas), freshman (vs all other class years), at a 2-year college (vs 4-year college), non-Hispanic Black (vs Hispanic or non-Hispanic White), or in a nonhealth major (vs health major) were less likely to be fully vaccinated. CONCLUSION: Given the disparities in COVID-19 vaccine coverage among college students, continued efforts are needed in this young, but important, population segment to address students' confidence in vaccines and to make vaccines more available and accessible on and near campuses. Novel approaches for tailored messaging and interventions to facilitate vaccine uptake may be needed for groups such as non-Hispanic Black students and students in rural areas who are less likely, compared with their counterparts, to accept COVID-19 vaccines.

A longitudinal study of SARS-CoV-2 antibody seroprevalence and mitigation behaviors among college students at an Arkansas University.

Objective: Assess university students' SARS-CoV-2 antibody seroprevalence and mitigation behaviors over time. Participants: Randomly selected college students (N = 344) in a predominantly rural Southern state. Methods: Participants provided blood samples and completed self-administered questionnaires at three timepoints over the academic year. Adjusted odds ratios and 95% confidence intervals were estimated from logistic regression analyses. Results: SARS-CoV-2 antibody seroprevalence was 18.2% in September 2020, 13.1% in December, and 45.5% in March 2021 (21% for those with no vaccination history). SARS-CoV-2 antibody seroprevalence was associated with large social gatherings, staying local during the summer break, symptoms of fatigue or rhinitis, Greek affiliation, attending Greek events, employment, and using social media as the primary COVID-19 information source. In March 2021, seroprevalence was associated with receiving at least one dose of a COVID-19 vaccination. Conclusion: SARS-CoV-2 seroprevalence was higher in this population of college students than previous studies. Results can assist leaders in making informed decisions as new variants threaten college campuses.

Characterization of a fatal methyl bromide exposure by analysis of the water cooler.

BACKGROUND: A suspected inhalation exposure to methyl bromide (MeBr) in the packaging and shipping area of a chemical manufacturer resulted in a worker fatality and several symptomatic cases. However, air testing was negative for MeBr resulting in uncertainty regarding the potential chemical exposure. Methods of quickly confirming the exposure and magnitude were sought. METHODS: Head space air and water samples were obtained from the breakroom water cooler in the facility and tested for MeBr. RESULTS: Increased levels of MeBr were identified in the air and water samples from the cooler and used to calculate the MeBr concentration of air entering the cooler. The MeBr air concentration within the breakroom was estimated as 1,200-2,100 ppm depending on assumptions regarding the amount of water dispensed from the cooler both before and during the incident. CONCLUSIONS: Estimated MeBr air concentrations in the breakroom were consistent with those known to be associated with reported health effects among the involved workers. The water cooler analysis represented a unique method of retrospectively verifying and quantifying exposure to MeBr.

Risk profiles for four types of work-related injury among hospital employees: a case-control study.

In this retrospective case-control study, researchers examined risk factors for four types of work-related injury (WRI) in hospital employees. Data were collected from employee health charts and computer databases (N = 2050) and analyzed using logistic regression. Study results showed that strain injuries were related to increased age, increased body mass index (BMI), and maintenance, custodial, and direct-caregiver employment types. Repetitive motion injuries were related to increased BMI and clerical and custodial employment types. Exposure/reaction injuries were related to increased age, increased BMI, and maintenance, custodial, and direct-caregiver employment types. Contact/assault injuries were related to increased age, increased BMI, and maintenance, custodial, and direct-caregiver employment types. All injury types were most often related to female gender and full-time employment status. Reformulating policies to improve screening, prevention, and education for those at risk for certain injury types may limit WRI occurrences and costs.

Factors associated with work-related injury among hospital employees: a case-control study.

The Central Arkansas Veterans Healthcare System (CAVHS) spends $1 million annually on occupational illnesses and injuries. To address the problem of injuries among hospital employees, a retrospective case-control study was conducted to examine select risk factors for work-related injuries (WRI) among CAVHS employees. Study methods included a review of employee health charts and computer and manual databases from 1997 to 2002 (N = 2,050). The researchers found that WRI increased with age; WRI occurred more often in women than in men; WRI was greater among maintenance and custodial staff compared to direct caregivers, and less among clerical staff; WRI occurred less often in part-time than full-time staff; and WRI increased with increasing body mass index. Developing standards, guidelines, and policies for preplacement screening, preventive measures, training, and education may help to minimize WRI and associated costs.

A review of the endocrine activity of parabens and implications for potential risks to human health.

Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible and appropriate, emphasis is placed on direct comparisons with human data with either 17beta-estradiol or DES, since this does not require extrapolation from animal data with the uncertainties inherent in such comparisons. Based on these comparisons using worst-case assumptions pertaining to total daily exposures to parabens and dose/potency comparisons with both human and animal no-observed-effect levels (NOELs) and lowest-observed-effect levels (LOELs) for estrogen or DES, it is biologically implausible that parabens could increase the risk of any estrogen-mediated endpoint, including effects on the male reproductive tract or breast cancer. Additional analysis based on the concept of a hygiene-based margin of safety (HBMOS), a comparative approach for assessing the estrogen activities of weakly active EACs, demonstrates that worst-case daily exposure to parabens would present substantially less risk relative to exposure to naturally occurring EACs in the diet such as the phytoestrogen daidzein.

Occupational asthma symptoms and respiratory function among aerial pesticide applicators.

BACKGROUND: Pesticide exposure has been suggested as one causal factor for the rise in asthma prevalence. The goal of this investigation was to determine the effect of pesticide exposure on respiratory symptoms and lung function in workers with occupational exposure to pesticides. METHODS: A prospective, case-controlled study was conducted among pesticide aviators (AV) and community controls (Con). In Phase I, subjects completed an asthma survey and baseline spirometry. In Phase II, subjects reported symptoms, lung function monitoring, and pesticide exposure during two, 14-day periods. RESULTS: Phase I-Self-reported asthma and symptoms were similar among AV (n = 135) and Con (n = 118) with 4-6% prevalence reported but with higher rates among smokers. Baseline lung function was similar; although, a higher proportion of AV had forced expiratory volume in one second (FEV(1)) <80% predicted (8% vs. 2%, P = 0.02). Phase II-Self-reported symptoms were similar with 80% of AV (n = 50) and 73% of Con (n = 49) reporting no symptoms. Only 4% of AV and 6% of controls reported increased symptoms from baseline to spray season. Serial lung function did not differ between group and mean diurnal variation in peak expiratory flow improved in both groups between sampling times (AV 18% vs. 14%; Con 19% vs. 16%, P < 0.001). CONCLUSIONS: This study suggests that among workers with occupational pesticide exposure, asthma symptoms and lung function are similar to those of controls with only community-based exposure.