Problem formulation for risk assessment of combined exposures to chemicals and other stressors in humans

When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors. As part of the HESI Risk Assessment in the 21st Century (RISK21) Project, a framework for CRA was developed in which problem formulation plays a critical role. The focus of this effort is primarily on a chemical CRA (i.e., two or more chemicals) with subsequent consideration of non-chemical stressors, defined as "modulating factors" (ModFs). Problem formulation is a systematic approach that identifies all factors critical to a specific risk assessment and considers the purpose of the assessment, scope and depth of the necessary analysis, analytical approach, available resources and outcomes, and overall risk management goal. There are numerous considerations that are specific to multiple stressors, and proper problem formulation can help to focus a CRA to the key factors in order to optimize resources. As part of the problem formulation, conceptual models for exposures and responses can be developed that address these factors, such as temporal relationships between stressors and consideration of the appropriate ModFs

Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible

Abstract Developments in the understanding of the etiology of cancer have undermined the 1970s concept that chemicals are either "carcinogens" or "non-carcinogens". The capacity to induce cancer should not be classified in an inflexible binary manner as present (carcinogen) or absent (non-carcinogen). Chemicals may induce cancer by three categories of mode of action: direct interaction with DNA or DNA replication including DNA repair and epigenetics; receptor-mediated induction of cell division; and non-specific induction of cell division. The long-term rodent bioassay is neither appropriate nor efficient to evaluate carcinogenic potential for humans and to inform risk management decisions. It is of questionable predicitiveness, expensive, time consuming, and uses hundreds of animals. Although it has been embedded in practice for over 50 years, it has only been used to evaluate less than 5% of chemicals that are in use. Furthermore, it is not reproducible because of the probabilisitic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design. The modes of action that lead to the induction of tumors are already considered under other hazardous property categories in classification (Mutagenicity/Genotoxicity and Target Organ Toxicity); a separate category for Carcinogenicity is not required and provides no additional public health protection

The importance of the intensive care unit environment in sleep-A study with healthy participants

Sleep disruption is common among intensive care unit patients, with potentially detrimental consequences. Environmental factors are thought to play a central role in ICU sleep disruption, and so it is unclear why environmental interventions have shown limited improvements in objectively assessed sleep. In critically ill patients, it is difficult to isolate the influence of environmental factors from the varying contributions of non-environmental factors. We thus investigated the effects of the ICU environment on self-reported and objective sleep quality in 10 healthy nurses and doctors with no history of sleep pathology or current or past ICU employment participated. Their sleep at home, in an unfamiliar environment ('Control'), and in an active ICU ('ICU') was evaluated using polysomnography and the Richard-Campbell Sleep Questionnaire. Environmental sound, light and temperature exposure were measured continuously. We found that the control and ICU environment were noisier and warmer, but not darker than the home environment. Sleep on the ICU was perceived as qualitatively worse than in the home and control environment, despite relatively modest effects on polysomnography parameters compared with home sleep: mean total sleep times were reduced by 48 min, mean rapid eye movement sleep latency increased by 45 min, and the arousal index increased by 9. Arousability to an awake state by sound was similar. Our results suggest that the ICU environment plays a significant but partial role in objectively assessed ICU sleep impairment in patients, which may explain the limited improvement of objectively assessed sleep after environmental interventions

Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study

Introduction: The prevalence of polycystic ovary syndrome (PCOS) is 10–15% in women of reproductive age. Its characteristics are (i) clinical or biochemical hyperandrogenism, (ii) oligomenorrhea or amenorrhea, and (iii) polycystic ovaries on ultrasound. PCOS is associated with lower quality of life, depression, anxiety, diabetes, and cardiovascular disease. Treatment commonly entails oral contraceptive use to lower endogenous androgen levels. Androgen levels and comorbidities may affect sexual function. Previous studies have addressed a limited range of possible contributing factors. We will assess sexual function as well as genital and self-reported sexual arousal in a laboratory setting in women with PCOS compared to an age-matched healthy control group. Modulation by biopsychosocial factors mentioned will be studied. Methods: This is a multicenter prospective case control study. The study population includes healthy women with and without PCOS, aged 18–40 years, in a stable heterosexual relationship for at least 6 months. Power is calculated at 67 participants in each group. Anticipating a drop out of 10%, 150 participants will be recruited. Main outcome measures: The main outcomes measured are sexual function using the Female Sexual Function Index, Sexual Desire Inventory, and Female Sexual Distress Scale-Revised; genital sexual arousal measured as vaginal pulse amplitude; and self-reported sexual arousal in response to erotic stimuli in a laboratory setting. The mediators that will be investigated include testosterone, free androgen levels, oral contraceptive use, sensitivity to androgens (using CAG repeat length), body mass index, body image, mental health, and self-esteem. Conclusion: Strengths of this study are the inclusion of a broad range of biopsychosocial outcome measures including DNA analysis, a healthy control group, and standardized assessment of genital and self-reported sexual arousal in a laboratory setting. With the design of this study we aim to provide an insight into which biopsychosocial factors associated with PCOS are related to sexual function, and how sexual function may be affected by treatment. These new insights may help to improve clinical management of PCOS while improving the quality of life. Pastoor H, Both S, Timman R, et al. Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study. Sex Med 2020;XX:XXX–XXX

Correction to:Positron emission tomography in the diagnosis and follow-up of transthyretin amyloid cardiomyopathy patients: A systematic review (European Journal of Nuclear Medicine and Molecular Imaging, (2023), 51, 1, (93-109), 10.1007/s00259-023-06381-3)

The authors regret that the name of J. H. van ’t Oever was incorrectly presented as J. H. A. van ’t Oever in the original article. The original article has been corrected. The original article can be found at https://doi.org/10.1007/s00259-023-06381-3.</p