Racial and ethnic disparities in the refusal of surgical treatment in women 40 years and older with breast cancer in the USA between 2010 and 2017.

PURPOSE: Although surgical resection is the main modality of treatment for breast cancer, some patients elect to refuse the recommended surgery. We assessed racial and ethnic differences in women 40 years and older who received or refused to receive surgical treatment for breast cancer in the USA and whether racial disparities in mortality were affected by their differences in the prevalence of refusal for surgical treatment. METHODS: We studied 277,127 women with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) data and performed multivariable logistic regressions to investigate the association between surgery status of breast cancer and race/ethnicity. Additionally, we performed Cox regression analyses to determine the predictors of mortality outcomes. RESULTS: Of 277,127 patients with breast cancer, 1468 (0.53%) refused to receive the recommended surgical treatment in our cohort. Non-Hispanic Black women were 112% more likely to refuse the recommended surgical treatment for breast cancer compared to their non-Hispanic White counterparts [adjusted odds ratio: 2.12, 95% confidence interval (CI) 1.82-2.47]. Women who underwent breast-conserving surgery [hazards ratio (HR) 0.15, 95% CI 0.13-0.16] and mastectomy (HR 0.21, 95% CI 0.18-0.23) had lower hazard ratios of mortality as compared to women who refused the recommended treatment after adjusting for covariates. CONCLUSION: Race/ethnicity was associated with refusal for the recommended surgery, especially among non-Hispanic Black women. Also, surgery refusal was associated with a higher risk of all-cause and breast cancer-related mortality. These disparities stress the need to tailor interventions aimed at raising awareness of the importance of following physician recommendations among minorities.

Stability and Performance Study of Fluorescent Organosilica pH Nanosensors.

Long-term stability and function are key challenges for optical nanosensors operating in complex biological environments. While much focus is rightly placed on issues related to specificity, sensitivity, reversibility, and response time, many nanosensors are not capable of transducing accurate results over prolonged time periods. Sensors could fail over time due to the degradation of scaffold material, degradation of signaling dyes and components, or a combination of both. It is critical to investigate how such degradative processes affect sensor output, as the consequences could be severe. Herein, we used fluorescent core-shell organosilica pH nanosensors as a model system, incubating them in a range of common aqueous solutions over time at different temperatures, and then searched for changes in fluorescence signal, particle size, and evidence of silica degradation. We found that these ratiometric nanosensors produced stable optical signals after aging for 30 days at 37 °C in standard saline buffers with and without 10% fetal bovine serum, and without any evidence of material degradation. Next, we evaluated their performance as real-time pH nanosensors in bacterial suspension cultures, observing a close agreement with a pH electrode for control nanosensors, yet observing obvious deviations in signal based on the aging conditions. The results show that while the organosilica scaffold does not degrade appreciably over time, careful selection of dyes and further systematic investigations into the effects of salt and protein levels are required to realize long-term stable nanosensors.

Human Immunodeficiency Virus Pre-exposure Prophylaxis and Increased Incidence of Sexually Transmitted Infections in the United States.

BACKGROUND: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) decreases HIV transmission. Some studies have raised concerns about a potential association between the implementation of HIV PrEP and the growing incidence rates of sexually transmitted infections (STIs) in the United States. METHODS: We conducted a quasi-experimental (interrupted time series) analysis of STI (syphilis, gonorrhea, and chlamydia) rates before (2000-2012) and after (2013-2017) the implementation of HIV PrEP. We also performed correlations between HIV PrEP utilization and STI cases at the national (2012-2017) and state (2017) levels. We defined HIV PrEP utilization as the number of people taking tenofovir disoproxil fumarate/emtricitabine for HIV prevention. RESULTS: HIV PrEP implementation was associated with 25% (relative risk [RR] 1.254, 95% confidence interval [CI] 1.245-1.263; P < .001) and 26% (RR 1.260, 95% CI 1.257-1.264; P < .001) increases in syphilis and gonorrhea rates, respectively, and a 12% reduction in chlamydia rates (RR: 0.884, 95% CI 0.883-0.885; P < .001). HIV PrEP utilization was correlated with the numbers of syphilis, gonorrhea, and chlamydia cases (spearman coefficients 1.00, 0.94, and 0.94, respectively; P < .001, P < .01, and P < .01, respectively). At the state level, HIV PrEP was also correlated with the number of cases of syphilis, gonorrhea, and chlamydia (spearman coefficients 0.85, 0.81, and 0.85, respectively; Ps < .001 for all correlations). CONCLUSIONS: The implementation and utilization of HIV PrEP in the United States were associated with increased rates of STIs. Further studies to confirm these associations and to elucidate potential causes are needed.

Bionano Interactions of Organosilica Nanoparticles with Myeloid Derived Immune Cells.

Investigating the interactions between nanomaterials and the cells they are likely to encounter in vivo is a critical aspect of designing nanomedicines for imaging and therapeutic applications. Immune cells such as dendritic cells, macrophages, and myeloid derived suppressor cells have a frontline role in the identification and removal of foreign materials from the body, with interactions shown to be heavily dependent on variables such as nanoparticle size, charge, and surface chemistry. Interactions such as cellular association or uptake of nanoparticles can lead to diminished functionality or rapid clearance from the body, making it critical to consider these interactions when designing and synthesizing nanomaterials for biomedical applications ranging from drug delivery to imaging and biosensing. We investigated the interactions between PEGylated organosilica nanoparticles and naturally endocytic immune cells grown from stem cells in murine bone marrow. Specifically, we varied the particle size from 60 nm up to 1000 nm and investigated the effects of size on immune cell association, activation, and maturation with these critical gatekeeper cells. These results will help inform future design parameters for in vitro and in vivo biomedical applications utilizing organosilica nanoparticles.

Organosilica Nanosensors for Monitoring Spatiotemporal Changes in Oxygen Levels in Bacterial Cultures.

Oxygen plays a central role in aerobic metabolism, and while many approaches have been developed to measure oxygen concentration in biological environments over time, monitoring spatiotemporal changes in dissolved oxygen levels remains challenging. To address this, we developed a ratiometric core-shell organosilica nanosensor for continuous, real-time optical monitoring of oxygen levels in biological environments. The nanosensors demonstrate good steady state characteristics (KpSV = 0.40 L/mg, R2 = 0.95) and respond reversibly to changes in oxygen concentration in buffered solutions and report similar oxygen level changes in response to bacterial cell growth (Escherichia coli) in comparison to a commercial bulk optode-based sensing film. We further demonstrated that the oxygen nanosensors could be distributed within a growing culture of E. coli and used to record oxygen levels over time and in different locations within a static culture, opening the possibility of spatiotemporal monitoring in complex biological systems.

Column Agglutination Assay Using Polystyrene Microbeads for Rapid Detection of Antibodies against SARS-CoV-2.

Rapid serology platforms are essential in disease pandemics for a variety of applications, including epidemiological surveillance, contact tracing, vaccination monitoring, and primary diagnosis in resource-limited areas. Laboratory-based enzyme-linked immunosorbent assay (ELISA) platforms are inherently multistep processes that require trained personnel and are of relatively limited throughput. As an alternative, agglutination-based systems have been developed; however, they rely on donor red blood cells and are not yet available for high-throughput screening. Column agglutination tests are a mainstay of pretransfusion blood typing and can be performed at a range of scales, ranging from manual through to fully automated testing. Here, we describe a column agglutination test using colored microbeads coated with recombinant SARS-CoV-2 spike protein that agglutinates when incubated with serum samples collected from patients recently infected with SARS-CoV-2. After confirming specific agglutination, we optimized centrifugal force and time to distinguish samples from uninfected vs SARS-CoV-2-infected individuals and then showed concordant results against ELISA for 22 clinical samples, and also a set of serial bleeds from one donor at days 6-10 postinfection. Our study demonstrates the use of a simple, scalable, and rapid diagnostic platform that can be tailored to detect antibodies raised against SARS-CoV-2 and can be easily integrated with established laboratory frameworks worldwide.

The Development of Nanoparticles for the Detection and Imaging of Ovarian Cancers.

Ovarian cancer remains as one of the most lethal gynecological cancers to date, with major challenges associated with screening, diagnosis and treatment of the disease and an urgent need for new technologies that can meet these challenges. Nanomaterials provide new opportunities in diagnosis and therapeutic management of many different types of cancers. In this review, we highlight recent promising developments of nanoparticles designed specifically for the detection or imaging of ovarian cancer that have reached the preclinical stage of development. This includes contrast agents, molecular imaging agents and intraoperative aids that have been designed for integration into standard imaging procedures. While numerous nanoparticle systems have been developed for ovarian cancer detection and imaging, specific design criteria governing nanomaterial targeting, biodistribution and clearance from the peritoneal cavity remain key challenges that need to be overcome before these promising tools can accomplish significant breakthroughs into the clinical setting.

Review: Nanomaterials for Reactive Oxygen Species Detection and Monitoring in Biological Environments.

Reactive oxygen species (ROS) and dissolved oxygen play key roles across many biological processes, and fluorescent stains and dyes are the primary tools used to quantify these species in vitro. However, spatio-temporal monitoring of ROS and dissolved oxygen in biological systems are challenging due to issues including poor photostability, lack of reversibility, and rapid off-site diffusion. In particular, ROS monitoring is hindered by the short lifetime of ROS molecules and their low abundance. The combination of nanomaterials and fluorescent detection has led to new opportunities for development of imaging probes, sensors, and theranostic products, because the scaffolds lead to improved optical properties, tuneable interactions with cells and media, and ratiometric sensing robust to environmental drift. In this review, we aim to critically assess and highlight recent development in nanosensors and nanomaterials used for the detection of oxygen and ROS in biological systems, and their future potential use as diagnosis tools.

Modified Organosilica Core-Shell Nanoparticles for Stable pH Sensing in Biological Solutions.

Continuous monitoring using nanoparticle-based sensors has been successfully employed in complex biological systems, yet the sensors still suffer from poor long-term stability partially because of the scaffold materials chosen to date. Organosilica core-shell nanoparticles containing a mixture of covalently incorporated pH-sensitive (shell) and pH-insensitive (core) fluorophores is presented as a continuous pH sensor for application in biological media. In contrast to previous studies focusing on similar materials, we sought to investigate the sensor characteristics (dynamic range, sensitivity, response time, stability) as a function of material properties. The ratio of the fluorescence intensities at specific wavelengths was found to be highly sensitive to pH over a physiologically relevant range (4.5-8) with a response time of <100 ms, significantly faster than that of previously reported response times using silica-based particles. Particles produced stable, pH-specific signals when stored at room temperature for more than 80 days. Finally, we demonstrated that the nanosensors successfully monitored the pH of a bacterial culture over 15 h and that pH changes in the skin of mouse cadavers could also be observed via in vivo fluorescence imaging following subcutaneous injection. The understanding gained from linking sensor characteristics and material properties will inform the next generation of optical nanosensors for continuous-monitoring applications.