Exploring perceptions of and attitudes towards tanning with school children, parents/carers and educators in Wales: A mixed methods study protocol for the SunChat study.

BACKGROUND: Skin cancer comprises half of all cancers in England and Wales. Most skin cancers can be prevented with safer sun exposure. As over exposure as a child can greatly increase future skin cancer risk, early and accessible sun safety education and promotion of sun safe behaviours is critical. Scientists agree there is no such thing as a 'safe tan', yet the public, including children, often have positive perceptions of tanned skin. To protect against future skin cancer, it is important to understand and address these misconceptions. The Curriculum for Wales with its area for Health and Well-being, and autonomy for schools in designing curriculum content, presents an ideal way to facilitate this exploration. AIMS: Gather data regarding perceptions towards tanning to explore the perceived effects of a tan on health.Inform the development and testing of an educational toolkit for integration within the Curriculum for Wales to encourage positive health behaviours and attitudes of school children towards tanning and sun exposure. METHODS: SunChat is a mixed methods exploratory study comprising three work streams: Workshops with school children to understand their perceptions on tanning.An online multiple-choice survey with parents/carers to understand perceptions, attitudes and behaviours towards tanning both for themselves and their children.An informal focus group with primary school educators to explore challenges in engaging with the school community around the Health and Well-being Area in the Curriculum for Wales. DISCUSSION: To date, there has been no work in Wales exploring children's, parents/carers', and educators' perceptions of tanning and how healthier attitudes can be encouraged. This study will engage with participants to scope current perceptions on tanning and the perceived effects tanning has on health. Findings will feed into future toolkit and curriculum development for health in schools in Wales and beyond.

PRESOLRE: study protocol for a primary school-based, cluster randomised controlled trial of three sun exposure risk prevention strategies on Reunion Island.

INTRODUCTION: Reunion Island, a French overseas department, is located in the southern hemisphere, close to the Capricorn tropic. This island has a multicultural and multiethnic population of 860 000 inhabitants, a quarter of whom are at high risk of developing skin cancer due to intense ultraviolet radiation. Melanoma is responsible for the majority of skin cancer deaths. The early prevention of melanoma is based on sun protection in childhood, but French regulations are not adapted to the environmental conditions of this tropical region.The main objective of our study is to evaluate the effectiveness of three sun protection programs conducted in Reunionese primary schools through a pupil knowledge questionnaire. METHODS AND ANALYSIS: PRESOLRE is an interventional, open-label, cluster-randomised controlled trial, in four parallel arms, that is being conducted throughout 2022-2023 on Reunion Island. The trial design assumes an escalation interventional effect using: first, a control arm without proposed intervention (arm 1); second, an arm whose classes are encouraged to use the validated educational programme 'Living With the Sun' (LWS) (arm 2); third, an arm whose classes are encouraged to use both 'LWS' combined with 'Mission Soleil Réunion's sun protection awareness programme (arm 3); fourth, an arm benefiting from an intervention similar to arm 3, combined with the distribution of hats, sunglasses and sun creams (arm 4). In all, 1780 pupils from 18 classes of 20 pupils, on average, will be included. Randomisation applies to the classes of pupils (so defined as clusters). The primary outcome is based on the proportion of correct answers to the knowledge questions after the awareness programme, compared between the four arms using a linear mixed model with random intercept. ETHICS AND DISSEMINATION: The study obtained ethics approval in 2022 (ID: 2022-A00350-43). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05367180.

Knowledge, Attitudes, and Practices of Sun Exposure and Sun Protection among the Population of Kazakhstan: A Cross Sectional Study.

OBJECTIVE: The aims of this study were to assess knowledge, attitudes, and practices regarding sun exposure and sun protection among the population of Kazakhstan. METHOD: A cross sectional study was conducted by administering an online questionnaire via social networking sites to residents of Kazakhstan. The questionnaire was designed to determine demographic information as well as knowledge, attitudes and practices regarding sun exposure and sun protection. RESULT: The responses of 249 participants were analysed.  Descriptive tests, bivariate analyses, and multiple linear regression were used to statistically analyse the data. The mean age of the participants was 31.7 ± 11.5 (SD) years. Most participants were of Kazakh nationality (88.7%), female (71.0 %), urban residents (93.9 %), and possessed higher education degrees (88.0 %). The level of knowledge and attitudes were found to be moderate amongst the population whilst practices were determined to be low.  Knowledge (p=0.002), attitudes (p=0.002), female gender (p=0.002), and having children educated in school about sun safety (p=0.018) were significantly associated with improved sun-protective practices. CONCLUSION: This study has demonstrated low adoption of sun protective practices in the Kazakhstan population, despite the identification of certain characteristics associated with higher rates of practice.

Sunscreen use and affordability attitudes based on ethnicity, socioeconomic status, and Fitzpatrick skin type.

IMPORTANCE: One in five Americans will develop skin cancer during their lifetime. While use of sunscreen can help prevent the development cutaneous cancer, regular use remains low nationwide. OBJECTIVE: To assess and better understand health care consumer preferences for sun protection products and perceived product accessibility and availability based on socioeconomic factors, race, and ethnicity. DESIGN: This quantitative survey study was conducted March through June of 2023. SETTING: Participants were recruited from two university family medicine clinical sites in the Buffalo, New York area, one located in a low and one located in a middle-to-upper socioeconomic neighborhood. PARTICIPANTS: Eligible participants were 18 years or older, fluent in English, and residents of the Buffalo, New York area. Surveys and consent forms were distributed by scripted verbal invitation, inviting all clinic patients who met eligibility criteria to participate. Participants were asked to self-report their racial/ethnic group as well as other demographic information including age, gender identification, household income, and household size. Information regarding sun exposure behaviors, and affordability/access was obtained using a combination of multiple choice and yes/no questions. A total of 405 participants were recruited. After excluding 235 incomplete responses, 170 surveys were available for analysis. INTERVENTIONS: None. MAIN OUTCOMES AND MEASURES: Our study aim was to expose health care consumer preferences as well as barriers to access based on socioeconomic factors, race, and ethnicity. RESULTS: Using a 25-question anonymous survey, 405 participants from two university family medicine clinical sites representing low- and middle-to-high-income neighborhoods, participated in the survey. 170 participants completed the survey questions and were included for analysis. Of those, 61.8% identified as female, 37.6% as male, and 0.6% as other. 51.2% of participants identified as lower income, 38.2% as middle-income, and 10.6% as upper income. The results of the survey revealed disparities in sunscreen use and affordability perceptions across demographic groups. Compared with Hispanics, Caucasians exhibited higher rates of sunscreen use (85 Caucasians, 7 Hispanics; p = 0.0073), prioritized SPF (95 Caucasians, 10 Hispanics; p = 0.0178), and were more likely to perceive sunscreen as unaffordable (6 Caucasians, 4 Hispanics; p = 0.0269). Analysis by Fitzpatrick Skin Type demonstrated differences in sunscreen utilization, with Types I-III using more compared to Types IV-VI (70 Types I-III, 51 Types IV-VI; p = 0.0173); additionally, Type I-III individuals were significantly more likely to cite cost as barrier to sunscreen purchase (40 Type I-III, 65 Types IV-VI; p < 0.0001). Moreover, lower-income individuals were significantly more likely to perceive sunscreen as unaffordable (12 lower-income, 1 middle & upper income; p = 0.0025) and cited cost as a barrier to purchase (46 lower-income, 59 middle & upper income; p = 0.0146) compared to middle-to-upper income counterparts. Though statistical significance was not established, respondents from middle & upper income groups reported higher sunscreen usage rates compared with their lower-income peers. CONCLUSIONS AND RELEVANCE: These findings highlight the importance of socioeconomic factors and ethnicity on accessibility to sunscreen and the impact of disparities in utilization among different ethnic and socioeconomic groups.

The Knowledge, Attitudes, and Practices of Parents Regarding Sun Protection for Their Children.

OBJECTIVE: To evaluate the knowledge, attitudes, and practices of parents toward protecting their children against skin cancer and the sun. METHODS: This cross-sectional study was performed in Turkey from March through October 2022. The authors used a questionnaire investigating the parents' and children's characteristics, attitudes, and practices toward sun protection and the Skin Cancer and Sun Knowledge (SCSK) scale to collect data. RESULTS: Of 465 parents, 60.2% were women, 83.2% were light-skinned, 20.2% perceived their children as risk-free, 43.8% perceived their children as low risk in terms of skin cancer, 14.6% examined their children from head to foot, 62.3% applied sunscreen to their children, 9.7% made them wear long-sleeved clothing, 60.0% made them wear headgear, 61.1% made them remain in the shade or under a sunshade, and 32.3% made them wear sunglasses. The mean parental SCSK scale score was 14.3 ± 4.1. Scale scores were higher among those who perceived their children as being at high risk for skin cancer (P = .000), whose children had not experienced red or painful sunburn in the previous year (P = .000), and who informed their children about sun protection (P = .000). CONCLUSIONS: Although knowledge of skin cancer and solar protection was high, parental perception of the risk of skin cancer was very low, and attitudes toward skin examination were also very relaxed.

Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

Perception of skin cancer risk and sun protective practices in individuals with vitiligo: a prospective international cross-sectional survey.

Many individuals with vitiligo are uncertain about their skin cancer risk, phototherapy risks, and recommended sun protective practices. This study examined the perceived skin cancer risk and sun protective practices among individuals living with vitiligo. A secondary objective was to understand where participants obtain this information. This was a prospective cross-sectional study. An online survey was distributed to vitiligo support group leaders globally who shared the survey with their members. Individuals over the age of 18 and with vitiligo were included. There were 209 survey respondents, the majority were between the ages 35-54 (45.5%, n = 95), female (70.8%, n = 148), White (66.0%, n = 138). Nearly half of respondents believed they were at increased risk of skin cancer because of their vitiligo (45.5%, n = 95) and nearly a quarter (22.5%, n = 47) believed that phototherapy increased their risk of skin cancer. Having vitiligo affected sun protective practices with less than a quarter (24.4%, n = 51) of respondents using sunscreen daily or often prior to their vitiligo diagnosis in comparison to the majority of respondents (60.3%, n = 126) using it after their vitiligo diagnosis. The three most common sources where patients obtained information were the internet and social media (46.4%, n = 97), vitiligo support groups (23.4%, n = 49), and dermatologists (20.6%, n = 43). Despite evidence indicating a decreased risk of skin cancer in individuals with vitiligo and supporting the safety of narrowband ultraviolet B phototherapy, many participants believed they were at an increased risk of skin cancer. Findings were sub-stratified and showed differences in sunscreen usage based on gender, skin color, and percent depigmentation. This study also found nearly half of respondents obtained information related to vitiligo from the internet and social media. The number of participants may limit the generalizability of the findings. Survey questionnaires are also subject to response bias. The findings from this study highlight demographic variations in sunscreen usage which may help guide the development of targeted interventions to improve sun protective behaviors among diverse populations with vitiligo. In addition, this study suggests certain sun protective practices and skin cancer risk perceptions may vary based on extent of depigmentation. Lastly, this study also demonstrates the internet and social media as a popular source for obtaining information, emphasizing the need for dermatologists to leverage various online communication channels to help disseminate accurate information.

[Screening for cutaneous melanoma: little impact, major challenges]. / Dépistage du mélanome : peu d'impact, beaucoup de défis.

Routine screening for melanoma has never been shown to be effective. Here, we revisit this debate and the preconceived notion that the increased detection of early-stage melanoma should necessarily be followed within the same population by a reduction in the incidence of advanced stages, which is not supported by any evidence. The issue of overdiagnosis, which has been debated for several decades, is discussed in the light of screening practices. We illustrate with two of its common motives, why this practice is ineffective. Finally, we suggest that the risk of overdiagnosis has probably reached its climax over the last two decades, as the increasing sensitivity of skin-imaging tools has not been followed by a refinement of histopathologic diagnostic criteria.

Le dépistage systématique du mélanome n'a jamais fait la preuve de son efficacité. Nous rediscutons ici de cette question en revenant sur l'idée reçue que le dépistage accru des stades précoces de mélanome au sein d'une population devrait engendrer une diminution des formes avancées de la maladie, ce qui ne se vérifie pas dans les faits. La question débattue depuis plusieurs décennies du surdiagnostic est également discutée à la lumière des pratiques de dépistage. Nous illustrons par deux motifs fréquents de dépistage pourquoi cette pratique est inefficace. Nous suggérons que le risque de surdiagnostic a atteint son paroxysme au cours des deux dernières décennies dans la mesure où la sensibilité croissante des outils d'imagerie cutanée n'a pas été suivie d'un affinement des critères diagnostiques histopathologiques.

Effect of education on sun-safe behaviour in kidney transplant recipients.

BACKGROUND: Organ transplant recipients (OTR) are more likely to develop skin cancer than the general population. One of the main components of the exposome that triggers the development of skin tumours is solar ultraviolet (UV) radiation. To reduce the incidence of harmful consequences of sun exposure, sun protection education is needed for patients taking long-term immunosuppressive drugs. METHODS: In a previous study, we assessed the sun-safe behaviour of 221 OTR using a questionnaire before and after transplantation and personally educated the patients about proper sun protection. After the education, there were no further reminder presentations. Presently, the sun protection and sun seeking habits of the available 176 of these patients were questioned to assess the long-term effect of the previous sun protection education. RESULTS: Two-four years after the education, more patients wore hats and protected their skin with long-sleeved clothing than before the education. In terms of sun seeking habits, both occupational and recreational sun exposure decreased significantly. Significantly fewer people went on holiday after transplantation, but those who went on holiday spent significantly less time in the sun. CONCLUSION: The long-term positive effects of education can be seen both in the patients' sun protection and in their sun seeking habits. However, the long-term goal is to maintain these results and thereby reduce the likelihood of skin tumours and consequently the associated tumour death.

The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers.

The prevalence of two major types of skin cancer, melanoma and non-melanoma skin cancer, has been increasing worldwide. Skin cancer incidence is estimated to rise continuously over the next 20 years due to ozone depletion and an increased life expectancy. Chemotherapeutic agents could affect healthy cells, and thus may be toxic to them and cause numerous side effects or drug resistance. Phytochemicals that are naturally occurring in fruits, plants, and herbs are known to possess various bioactive properties, including anticancer properties. Although the effects of phytochemicals are relatively milder than chemotherapeutic agents, the long-term intake of phytochemicals may be effective and safe in preventing tumor development in humans. Diverse phytochemicals have shown anti-tumorigenic activities for either melanoma or non-melanoma skin cancer. In this review, we focused on summarizing recent research findings of the natural and dietary terpenoids (eucalyptol, eugenol, geraniol, linalool, and ursolic acid) that have anticancer activities for both melanoma and non-melanoma skin cancers. These terpenoids may be helpful to protect skin collectively to prevent tumorigenesis of both melanoma and nonmelanoma skin cancers.

[Prevention and health promotion in dermatology]. / Prävention und Gesundheitsförderung in der Dermatologie.

The term prevention includes measures that are used to avoid illnesses or damage to health as well as to reduce the risk of illness or to delay its occurrence. Preventive measures can be classified based on various criteria: temporal differentiation (primary, secondary, and tertiary prevention), context (behavioral and relational prevention), and recipient (general and individual prevention). Health promotion is used when appropriate measures are intended to strengthen and increase human health potential and resources. This includes, among other things, measures to develop health-promoting behavior (empowerment) and measures regarding the planning and implementation of health-promoting behavior (participation). One goal of these measures is generally to increase health literacy. This article describes examples of prevention and health promotion measures for occupational skin cancer (counseling approach for individual sun protection for outdoor workers; "individuelle Lichtschutzberatung" [ILB]) as well as occupational hand eczema within the meaning of German occupational disease number 5101 (outpatient and inpatient individual prevention measures). These are supplemented by the example of outpatient age-adapted small group trainings for patients with atopic dermatitis according to the multicenter evaluated concept of AGNES e. V. ("Arbeitsgemeinschaft Neurodermitisschulung") and ARNE ("Arbeitsgemeinschaft Neurodermitisschulung im Erwachsenenalter"). These examples also address aspects of sustainability and digitalization (eHealth, eLearning) in the areas of prevention and health promotion.

Skin cancer risk behaviors in sexual minority men: A mixed methods approach.

OBJECTIVE: Sexual minority men experience disproportionately elevated rates of skin cancers, likely driven by excess ultraviolet radiation exposure-namely through tanning behaviors. However, limited integrated theoretical models exist to explain sexual minority men's elevated skin cancer risk. The aim of the current study is to further test and refine an integrated theory of skin cancer risk behaviors among sexual minority men by incorporating minority stress into the integrated health behavior model of tanning. METHOD: The study employed a parallel mixed methods design, with a Phase 1 qualitative stage (N = 30) and a Phase 2 quantitative stage (Model 1: N = 320; Model 2: N = 319). In both phases, participants were sexual minority men, equally stratified as those with versus without recent tanning exposure and were recruited from across the United States. RESULTS: Qualitative and quantitative data supported the overall integrated model, with some quantitative paths varying depending on the tanning behavior outcome. Overall, appearance-related motives to tan and beliefs that tanning regulates affect emerged as the most consistent proximal predictors. Minority stress significantly predicted holding more positive attitudes toward tanning as an effective affect regulation strategy. CONCLUSIONS: The results from this mixed methods study support the inclusion of minority stressors into the adapted integrative health behavior model of tanning. Replication within prospective designs would strengthen the evidence for this model, which may be helpful in guiding future skin cancer prevention programs tailored to sexual minority men. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Melanoma-associated melanocortin 1 receptor variants confer redox signaling-dependent protection against oxidative DNA damage.

Cutaneous melanoma, a lethal skin cancer, arises from malignant transformation of melanocytes. Solar ultraviolet radiation (UVR) is a major environmental risk factor for melanoma since its interaction with the skin generates DNA damage, either directly or indirectly via oxidative stress. Pheomelanin pigments exacerbate oxidative stress in melanocytes by UVR-dependent and independent mechanisms. Thus, oxidative stress is considered to contribute to melanomagenesis, particularly in people with pheomelanic pigmentation. The melanocortin 1 receptor gene (MC1R) is a major melanoma susceptibility gene. Frequent MC1R variants (varMC1R) associated with fair skin and red or yellow hair color display hypomorphic signaling to the cAMP pathway and are associated with higher melanoma risk. This association is thought to be due to production of photosensitizing pheomelanins as well as deficient induction of DNA damage repair downstream of varMC1R. However, the data on modulation of oxidative DNA damage repair by MC1R remain scarce. We recently demonstrated that varMC1R accelerates clearance of reactive oxygen species (ROS)-induced DNA strand breaks in an AKT-dependent manner. Here we show that varMC1R also protects against ROS-dependent formation of 8-oxodG, the most frequent oxidative DNA lesion. Since the base excision repair (BER) pathway mediates clearance of these DNA lesions, we analyzed induction of BER enzymes in human melanoma cells of varMC1R genotype. Agonist-mediated activation of both wildtype (wtMC1R) and varMC1R significantly induced OGG and APE-1/Ref1, the rate-limiting BER enzymes responsible for repair of 8-oxodG. Moreover, we found that NADPH oxidase (NOX)-dependent generation of ROS was responsible for AKT activation and oxidative DNA damage repair downstream of varMC1R. These observations provide a better understanding of the functional properties of melanoma-associated MC1R alleles and may be useful for the rational development of strategies to correct defective varMC1R responses for efficient photoprotection and melanoma prevention in fair-skinned individuals.

Exploring the role of cancer fatalism and engagement with skin cancer genetic information in diverse primary care patients.

OBJECTIVE: To broaden the currently limited reach of genomic innovations, research is needed to understand how psychosocial and cultural factors influence reactions to genetic testing in diverse subgroups. Cancer fatalism is important in cancer prevention and deserves theoretical and empirical attention in the context of genomics and behavior change. METHODS: The current study employed data from a randomized controlled trial (N = 593) offering skin cancer genetic testing (using the melanocortin-1 receptor [MC1R] gene) in primary care in Albuquerque, New Mexico, USA. We examined interrelations of cancer fatalism with demographics, general health beliefs, perceived risk, perceived control, sun protection and skin screening behaviors and cancer worry in the skin cancer context stratified across Hispanic versus non-Hispanic ethnicity, and examined cancer fatalism as a moderator of intervention effects on study primary outcomes, including 3-month sun protection, cancer worry and perceived risk. RESULTS: Cancer fatalism was significantly related to the perception of control over skin cancer risk behaviors (ps ≤ 0.01) and demographics (ethnicity, education, health literacy; ps < 0.05), but not consistently related to general health beliefs or risk perception. Cancer fatalism did not moderate intervention effects on primary outcomes, except those with higher cancer fatalism randomized to intervention had higher levels of 3-month cancer worry (p = 0.019). CONCLUSIONS: These findings will guide future work considering the role of cancer fatalism in use of genomic technologies in the general population. This work anticipates strategies required to address cancer fatalism as translational genomics becomes more commonly available to diverse general population subgroups.

Betanin Attenuates Epigenetic Mechanisms and UV-Induced DNA Fragmentation in HaCaT Cells: Implications for Skin Cancer Chemoprevention.

Dermal photoaging refers to the skin's response to prolonged and excessive ultraviolet (UV) exposure, resulting in inflammation, changes to the tissue, redness, swelling, and discomfort. Betanin is the primary betacyanin in red beetroot (Beta vulgaris) and has excellent antioxidant properties. Yet, the specific molecular mechanisms of betanin in HaCaT cells have not been fully clarified. The objective of this study was to investigate the activity of betanin and the underlying mechanisms in HaCaT cells; furthermore, in this study, we explored the protective effect of various concentrations of betanin against UVB irradiation on HaCaT cells. Additionally, we assessed its influence on the transcription of various epigenetic effectors, including members of the DNA methyltransferase (DNMT) and histone deacetylase (HDAC) families. Our findings demonstrate a notable downregulation of genes in HaCaT cells, exhibiting diverse patterns upon betanin intake. We considered the involvement of DNMT and HDAC genes in distinct stages of carcinogenesis and the limited exploration of the effects of daily exposure dosages. Our results indicate that betanin may protect the skin from damage caused by UV exposure. Further investigation is essential to explore these potential associations.

Current insights and future perspectives of ultraviolet radiation (UV) exposure: Friends and foes to the skin and beyond the skin.

Ultraviolet (UV) radiation is ubiquitous in the environment, which has been classified as an established human carcinogen. As the largest and outermost organ of the body, direct exposure of skin to sunlight or UV radiation can result in sunburn, inflammation, photo-immunosuppression, photoaging and even skin cancers. To date, there are tactics to protect the skin by preventing UV radiation and reducing the amount of UV radiation to the skin. Nevertheless, deciphering the essential regulatory mechanisms may pave the way for therapeutic interventions against UV-induced skin disorders. Additionally, UV light is considered beneficial for specific skin-related conditions in medical UV therapy. Recent evidence indicates that the biological effects of UV exposure extend beyond the skin and include the treatment of inflammatory diseases, solid tumors and certain abnormal behaviors. This review mainly focuses on the effects of UV on the skin. Moreover, novel findings of the biological effects of UV in other organs and systems are also summarized. Nevertheless, the mechanisms through which UV affects the human organism remain to be fully elucidated to achieve a more comprehensive understanding of its biological effects.