Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions.

The integration of nanomaterials (NMs) into an ever-expanding number of daily used products has proven to be highly desirable in numerous industries and applications. Unfortunately, the same "nano" specific physicochemical properties, which make these materials attractive, may also contribute to hazards for individuals exposed to these materials. In 2021, it was estimated that 7 out of 10 deaths globally were accredited to chronic diseases, such as chronic liver disease, asthma, and cardiovascular-related illnesses. Crucially, it is also understood that a significant proportion of global populace numbering in the billions are currently living with a range of chronic undiagnosed health conditions. Due to the significant number of individuals affected, it is important that people suffering from chronic disease also be considered and incorporated in NM hazard assessment strategies. This review examined and analyzed the literature that focused on NM-induced adverse health effects in models which are representative of individuals exhibiting pre-existing medical conditions with focus on the pulmonary, cardiovascular, hepatic, gastrointestinal, and central nervous systems. The overall objective of this review was to outline available data, highlighting the important role of pre-existing disease in NM-induced toxicity with the aim of establishing a weight of evidence approach to inform the public on the potential hazards posed by NMs in both healthy and compromised persons in general population.

Particulate and drug-induced toxicity assessed in novel quadruple cell human primary hepatic disease models of steatosis and pre-fibrotic NASH.

In an effort to replace, reduce and refine animal experimentation, there is an unmet need to advance current in vitro models that offer features with physiological relevance and enhanced predictivity of in vivo toxicological output. Hepatic toxicology is key following chemical, drug and nanomaterials (NMs) exposure, as the liver is vital in metabolic detoxification of chemicals as well as being a major site of xenobiotic accumulation (i.e., low solubility particulates). With the ever-increasing production of NMs, there is a necessity to evaluate the probability of consequential adverse effects, not only in health but also in clinically asymptomatic liver, as part of risk stratification strategies. In this study, two unique disease initiation and maintenance protocols were developed and utilised to mimic steatosis and pre-fibrotic NASH in scaffold-free 3D liver microtissues (MT) composed of primary human hepatocytes, hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. The characterized diseased MT were utilized for the toxicological assessment of a panel of xenobiotics. Highlights from the study included: 1. Clear experimental evidence for the pre-existing liver disease is important in the augmentation of xenobiotic-induced hepatotoxicity and 2. NMs are able to activate stellate cells. The data demonstrated that pre-existing disease is vital in the intensification of xenobiotic-induced liver damage. Therefore, it is imperative that all stages of the wide spectrum of liver disease are incorporated in risk assessment strategies. This is of significant consequence, as a substantial number of the general population suffer from sub-clinical liver injury without any apparent or diagnosed manifestations.

The Association of Work-related Stress According to the Demand-Control Model With Aggravation of Pre-existing Disease During the First State of COVID-19 Emergency in Japan.

BACKGROUND: The job environment has changed a lot during the period of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the association between work-related stress and aggravation of pre-existing disease in workers during the first state of COVID-19 emergency in Japan. METHODS: Data were obtained from a large internet survey conducted between August 25 and September 30, 2020 in Japan. Participants who reported that they had a job as well as current history of disease(s) (ie, pre-existing conditions) were included (n = 3,090). Aggravation of pre-existing disease during the state of emergency was self-reported. Work-related stress from April 2020 (since the state of COVID-19 emergency) was assessed according to a job demand-control model. Multivariable logistic regression models were used to analyze the association. RESULTS: Aggravation of pre-existing diseases was reported by 334 participants (11%). The numbers of participants with high demand and low control were 112 (18%) and 100 (14%), respectively. Compared to medium demand, high demand was significantly associated with aggravation of pre-existing diseases (odds ratio 1.77; 95% confidence interval, 1.30-2.42). Low control compared to medium control was also significantly associated with aggravation of pre-existing diseases (odds ratio 1.39; 95% confidence interval, 1.02-1.92). CONCLUSION: Work-related stress during the first state of COVID-19 emergency was associated with aggravation of pre-existing disease during that period.

[Changes in age distribution and frequency of comorbidities in patients in the occupational insurance association treatment process]. / Veränderung der Altersstruktur und Häufigkeit von Komorbiditäten bei Patienten im bg-lichen Heilverfahren.

BACKGROUND: Due to the demographic development the proportion of older patients has increased. These show at least a higher rate of comorbidities, which affects the length of inpatient hospital stay. Until now no uniform recording exists for such comorbidities within the occupational insurance association system even if the clinical relevance is beyond dispute. Adaptations within the system with increased interdisciplinary treatment are necessary. OBJECTIVE: The aim of this study was to analyze changes in the age distribution and the frequency of comorbidities in patients in the occupational insurance association system. METHODS: The study was a retrospective analysis of age distribution and comorbidities of all operatively treated occupational insurance association patients in 2005 (n = 631), 2010 (n = 1180) and 2015/2016 (n = 2315). A comparison of the age groups ≤29 years, 30-49 years, 50-65 years and ≥66 years was performed. RESULTS: The proportion of patients aged 50-65 years showed a significant increase: 2005 (26.5%), 2010 (30.5%) and 2015/2016 (37.3%) (p < 0.001) and an increased proportion of patients with at least 1 comorbidity: 2005 (38.7%), 2010 (52.5%) and 2015/2016 (52.9%) (p = 0.01). This was statistically significant (p < 0.001, p = 0.005) within the age group 30-49 years (2005: 31.1%, 2015/2016: 49.0%) and the age group 50-65 years (2005: 55.7%, 2015/2016: 67.1%). Significant changes were found for arterial hypertension, morbid obesity, thyroid and respiratory diseases. In addition, there was an increase in multimorbid patients. DISCUSSION: A changing age distribution with a tendency to an increased number of older patients and an increased frequency of comorbidities could be determined. In the present documentation system of the occupational insurance association treatment procedure these comorbidities are insufficiently recorded and considered, even though their clinical relevance is indisputable. Adaptations with respect to intensified interdisciplinary cooperation are necessary.

As We Drink and Breathe: Adverse Health Effects of Microcystins and Other Harmful Algal Bloom Toxins in the Liver, Gut, Lungs and Beyond.

Freshwater harmful algal blooms (HABs) are increasing in number and severity worldwide. These HABs are chiefly composed of one or more species of cyanobacteria, also known as blue-green algae, such as Microcystis and Anabaena. Numerous HAB cyanobacterial species produce toxins (e.g., microcystin and anatoxin-collectively referred to as HAB toxins) that disrupt ecosystems, impact water and air quality, and deter recreation because they are harmful to both human and animal health. Exposure to these toxins can occur through ingestion, inhalation, or skin contact. Acute health effects of HAB toxins have been well documented and include symptoms such as nausea, vomiting, abdominal pain and diarrhea, headache, fever, and skin rashes. While these adverse effects typically increase with amount, duration, and frequency of exposure, susceptibility to HAB toxins may also be increased by the presence of comorbidities. The emerging science on potential long-term or chronic effects of HAB toxins with a particular emphasis on microcystins, especially in vulnerable populations such as those with pre-existing liver or gastrointestinal disease, is summarized herein. This review suggests additional research is needed to define at-risk populations who may be helped by preventative measures. Furthermore, studies are required to develop a mechanistic understanding of chronic, low-dose exposure to HAB toxins so that appropriate preventative, diagnostic, and therapeutic strategies can be created in a targeted fashion.