Effects of Particle Size and Surface Charge on Mutagenicity and Chicken Embryonic Toxicity of New Silver Nanoclusters.

Though there are many toxicological studies on metal nanoparticles (NPs), it remains difficult to explain discrepancies observed between studies, largely due to the lack of positive controls and disconnection between physicochemical properties of nanomaterials with their toxicities at feasible exposures in a specified test system. In this study, we investigated effects of particle size and surface charge on in vitro mutagenic response and in vivo embryonic toxicity for newly synthesized silver nanoclusters (AgNCs) at human or environmental relevant exposure and compared the new findings with one of the most common nanoscale particles, titanium dioxide NPs (TiO2 NPs as a positive control). We hypothesized that the interaction of the test system and physicochemical properties of nanomaterials are critical in determining their toxicities at concentrations relevant with human or environmental exposures. We assessed the mutagenicity of the AgNCs (around 2 nm) and two sizes of TiO2 NPs (i.e., small: 5-15 nm, big: 30-50 nm) using a Salmonella reverse mutation assay (Ames test). The smallest size of AgNCs showed the highest mutagenic activity with the Salmonella strain TA100 in the absence and presence of the S9 mixture, because the AgNCs maintained the nano-size scale in the Ames test, compared with two other NPs. For TiO2 NPs, the size effect was interfered by the agglomeration of TiO2 NPs in media and the generation of oxidative stress from the NPs. The embryonic toxicity and the liver oxidative stress were evaluated using a chicken embryo model at three doses (0.03, 0.33, and 3.3 µg/g egg), with adverse effects on chicken embryonic development in both sizes of TiO2 NPs. The non-monotonic response was determined for developmental toxicity for the tested NPs. Our data on AgNCs was different from previous findings on AgNPs. The chicken embryo results showed some size dependency of nanomaterials, but they were more well correlated with lipid peroxidation (malondialdehyde) in chicken fetal livers. A different level of agglomeration of TiO2 NPs and AgNCs was observed in the assay media of Ames and chicken embryo tests. These results suggest that the test nanotoxicities are greatly impacted by the experimental conditions and the nanoparticle's size and surface charge.

Comorbidity profiles of patients experiencing homelessness: A latent class analysis.

Individuals experiencing homelessness are known to have increased rates of healthcare utilization when compared to the average patient population, often attributed to their complex health care needs and under or untreated comorbid conditions. With increasing focus on hospital readmissions among acute care settings, a better understanding of these comorbidity patterns and their impacts on acute care utilization could help improve quality of care. This study aims to identify distinct comorbidity profiles of homeless patients, and to explore the correlates of the identified comorbidity profiles and their impact on hospital readmission. This is a retrospective analysis using electronic health records (EHR) of patients experiencing homelessness encountered in the hospitals of ChristianaCare from 2015 to 2019 (N = 3445). Latent class analysis (LCA) was used to identify the comorbidity profiles of homeless patients. The mean age of the study population was 44-year, and the majority were male (63%). The most prevalent comorbid conditions were tobacco use (77%), followed by depression (58%), drug use disorder (56%), anxiety disorder (50%), hypertension (44%), and alcohol use disorder (43%). The LCA model identified 4 comorbidity classes-"relatively healthy" class with 31% of the patients, "medically-comorbid with SUD" class with 15% of the patients, "substance use disorder (SUD)" class with 39%, and "Medically comorbid" class with 15% of the patients. The Kaplan-Meir curves of probability of readmission against time from the index visits were significantly different for the four classes (p<0.001). The multivariable Cox proportional hazard model adjusted for age, sex, race, ethnicity, and insurance type showed that the hazard for readmission among patients in medically comorbid with SUD class is 3.16 (CI: 2.72, 3.67) times higher than the patients in the relatively healthy class.

Factors Associated With Hospital Readmission Among Patients Experiencing Homelessness.

INTRODUCTION: Homelessness is associated with increased acute care utilization and poor healthcare outcomes. This study aims to compare hospital readmission rates among patients experiencing homelessness and patients who are not homeless and assess the impact of different clinical and demographic characteristics on acute care utilization among patients experiencing homelessness. METHODS: This was a retrospective study of patients encountered in 2018 and 2019 at ChristianaCare Health Systems. The analysis was done in August 2021. The prevalence of major chronic conditions among patients experiencing homelessness (n=1,329) and those not experiencing it (n=143,360) was evaluated. Patients experiencing homelessness were matched with nonhomeless patients using 1:1 propensity score matching. Time-to-event analysis approaches were used to analyze time-to-readmission and 30-day readmission rates. RESULTS: The 30-day readmission rates were 42.8% among patients experiencing homelessness and 19.9% among matched patients not experiencing homelessness. The hazard of 30-day readmission among patients experiencing homelessness was 2.6 (95% CI=1.93, 3.53) times higher than that among the matched nonhomeless cohort. In patients experiencing homelessness, drug use disorder, major depressive disorder, chronic kidney disease, obesity, arthritis, HIV/AIDS, and epilepsy were associated with shortened time to readmission. Moreover, Black racial identity was associated with shortened time to readmission. CONCLUSIONS: Patients experiencing homelessness had higher acute care utilization than those not experiencing homelessness. Black racial identity and several comorbidities were associated with increased acute care utilization among patients experiencing homelessness. Efforts to address upstream social determinants of health, destigmatization, and healthcare management accounting for the whole spectrum of clinical comorbidities might be important in promoting the health of people experiencing homelessness.

Use of Chicken Embryo Model in Toxicity Studies of Endocrine-Disrupting Chemicals and Nanoparticles.

Lab animals such as mice and rats are widely used in toxicity research of food additive and pharmaceutics, despite the well-recognized research limitation such as the inability to simulate human neurological diseases, faster absorption of chemicals, big variations among species, and high cost when using a large number of animals. The Society of Toxicology's guidance now focuses on minimizing discomfort and distress of lab animals, finding alternative ways to reduce animal number, replacing animals with in vitro models, and complying to the animal welfare policies. The chicken embryonic model can be a better alternative to mice and rats because of its abundant availability and cost-effectiveness. It can be studied in both laboratory and natural environment, with easy manipulation in ovo or in vivo. The objective of this review paper is to evaluate the use of chicken embryonic model in toxicity evaluation for endocrine-disrupting chemicals (EDCs) and nanoparticles (NPs) by different end points to determine more comprehensive toxic responses. The end points include chicken embryonic mortality and hatchability, developmental malformation analysis, hormonal imbalance, physiological changes in endocrine organs, and antiangiogenesis. Major research methodologies using chicken embryos are also summarized to demonstrate their versatile practice and valuable application in modern toxicity evaluation of EDCs and NPs.

Association between COVID-19 pandemic and the suicide rates in Nepal.

BACKGROUND: Past works have linked the COVID-19 pandemic and subsequent public health responses such as isolation, quarantine, and lockdown to increased anxiety, sleep disorders, depressive symptoms, and suicidal ideation. Only a few studies, mostly carried out in high-income countries, have investigated the association between the pandemic and suicide rate. We seek to investigate the changes in the monthly suicide rates during the COVID-19 pandemic in Nepal, compared to the pre-pandemic suicide rates. METHODS AND FINDINGS: This is a retrospective study investigating the changes in suicide rates in Nepal during the COVID-19 pandemic period (April 2020 to June 2021), compared to the pre-pandemic period (July 2017 to March 2020), adjusted for seasonality and long-term trend in the suicide rate. We performed analysis for the entire country as well as sub-sample analyses stratified by gender and provinces. A total of 24350 suicides deaths during four years of the study window were analyzed. We found an overall increase in the monthly suicide rate in Nepal with an average increase of 0.28 (CI: 0.12,0.45) suicide per 100,000 during the pandemic months. The increase in suicide rate was significant both among males (increase in rate = 0.26, CI: 0.02,0.50) and females (increase in rate = 0.30, CI: 0.18,0.43). The most striking increments in suicide rates were observed in June, July, and August 2020. The pattern of increased suicide rates faded away early on among males, but the effect was sustained for a longer duration among females. Sudurpaschim and Karnali provinces had the highest increase in suicide rates associated with the COVID-19 pandemic. CONCLUSIONS: The COVID-19 pandemic is associated with an increased suicide rate in Nepal. The findings may inform policymakers in designing appropriate public health responses to the pandemic that are considerate of the potential impact on mental health and suicide.